December 11, 2024 • 50 mins
Dr. Todd Gaines with Colorado State University joins us this week to talk about some novel genetic methods to control weeds! He covers the genomic timeline and how things have changed through the years, and how genomics helps understand herbicide resistance by identifying target site genes and mutations.
Some links that Dr. Gaines wanted to share:
https://link.springer.com/article/10.1186/s13059-024-03274-y
https://www.ingentaconnect.com/content/resinf/opm/2024/00000035/00000004/art00002
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Transcript
Episode Transcript
Available transcripts are automatically generated. Complete accuracy is not guaranteed.
Unknown (00:00):
Music.
Alyssa Essman (00:07):
Welcome back to the war against weeds podcast.
This is Alyssa Essman, WeedScience extension specialist at
the Ohio State and today I'mjoined by my co host, Dr Joe
Ikley at North Dakota StateUniversity. How's it going Joe?
Joe Ikley (00:19):
Not too bad, still relatively warm during the days.
So winter isn't here yet.
Alyssa Essman (00:28):
It's coming upon us rather quickly. I fear. Today
we're really excited to bejoined by Dr Todd Gaines,
professor at Colorado StateUniversity, to talk about a
really unique and interestingtopic, and that is, you know,
novel methods for for pigweedcontrol and kind of his area of
expertise. So, Todd, you want totell us a little bit about what
you do at Colorado State.
Todd Gaines (00:50):
Yeah. Hi Alyssa. Hi Joe. Thanks. It's great to chat
with you today. What I work on.I'm really interested in the
genetics of wheat, understandinghow they do what they do, and
why they're so successful, andno matter the very best ideas we
have to get rid of them andmanage them that they're always
seeming to come up with a way torespond and to understand that
(01:13):
from the genetics angle, whetherthat's herbicide resistance,
whether that's shifts Inemergence, you know, how can we
understand from their geneticdiversity background, how weeds
are responding to our managementpractices?
Alyssa Essman (01:29):
Awesome. So that's kind of a good place to
start. We have a question herefirst to kind of help give us
some background and maybe evensome resources. But I was
wondering if you could give ussome information on the
international weed GenomicsConsortium, maybe what it is,
and how you've been involvedwith that.
Todd Gaines (01:47):
Yeah, I'd like to start by going back a little bit
to sort of the start of thegenomics era for plant. You
know, we have the first plantthat had its genome assembled
and put together. So that's, youknow, the genome is the
collection of all the DNA, allthe genes and other structural
(02:07):
parts of the DNA that make up tochromosomes. And, of course,
that contains the instructionsfor how to make the plant. The
first one for the model plant,Arabidopsis. It's a little
mustard that it's kind of a wildplant and northern latitudes
around the world. That genomewas completed in the year 2000
and it's really interesting tothink that, you know,
(02:29):
altogether, that effort, youknow, probably cost somewhere
roughly in the range of tenmillion you know, in terms of
the sequencing and the time. Andit was a many, many year
project, and that genome stillcontinues to be updated, but
it's a really incrediblyvaluable reference for plant
biology, understanding at a verybasic level how plants work. And
(02:51):
then you zoom forward to, youknow, probably in the range of
about 10 years after that, a lotof people are starting to think,
could we do genomes for weedsand genomes for major crops were
getting done. You know, Rice wasdone, corn was done and
appointed there millet andpeople working on tomato and
(03:12):
soybean, wheat was a morechallenging one, a bigger genome
coming later. But certainly, youknow, you could see a lot of
value and reason to invest indoing these crop genomes, and
they were at that pointbecoming, you know, maybe multi
million dollar projects, butless than 10 million. So still,
you know, to do a weed species,very, very expensive. And so
(03:33):
there are a lot ofconversations, particularly at
the Weed Science meetings aroundmaybe, could we pick a model
weed and find the resources tomake that happen, and it really
never, kind of got moved out ofthat. Then we moved into the era
of next generation sequencing,as it's called, and this brought
an incredible drop in the costof getting DNA sequence. So it's
(03:57):
kind of like, you know, justlike the computer processors in
our computers get faster. Theysort of double in capacity about
every 18 months. There's thisthing called Moore's law that
sort of describes that, thatthey're going faster and faster
all the time. And you know that,right? If you have a two year
old computer, suddenly it'slike, why is this so slow, you
know? And you get a new one, andthat's essentially what
(04:19):
happened. There's thisincredible change in the
technology that now we could gethuge amounts of data and the
cost dropped by orders ofmagnitude. So then people could
start to work with the RNA, withthe expressed genes. And so we
can call that the transcriptome.Each RNA is called the
transcript, and those are,again, the instructions for the
(04:39):
genes that make the proteinsthat do everything in the plant.
And that really became feasiblefor weeds in the range of 10 to
12 years ago. And you startseeing people using that to
study herbicide resistance inparticular, start to find new
mutations for resistance forthings like group one you know,
your grass herbicides and. Andsome work was also done on group
(05:02):
four herbicides, the auxins. Butstill, it didn't give us a
picture of the whole genome, youknow, all the other information
in addition to the genes. Soagain, this is going along in
about 2016 there's aninternational Weed Science
meeting in Prague, and there's aworkshop there on weed genomics.
(05:22):
And so a lot of people wherethey're talking and thinking,
Okay, this cost has come down.We have these important weed
species. We see reasons why we'dwant to do this. That was when
people started thinking, howcould we actually make this
happen? And the idea cametogether that a lot of the crop
protection companies, you know,that discover and market
(05:43):
herbicides. They were doing someof this work, and a few of them
had maybe a genome or two, ormaybe some of these
transcriptomes. But of course,they had that information
themselves. They're using it fortheir own projects. And the
thought was, is there a way thatif these companies could come
together and pool some resourcesthat these genomes could get
(06:03):
done and then be shared with thewhole Weed Science community.
And that's that started the ballrolling on these conversations
and more workshops, moremeetings, and it was eventually
by actually in 2020. Was anotherkind of milestone into the first
really complete, well donegenome of what we call a real
(06:25):
weed was done. That washorseweed, can I say, conyza
canadensis, that was done by agroup from mag, Canada. And then
in that same year was when theplan really solidified for the
International weed GenomicsConsortium. So that brought
together the companies,including BASF, Bayer crop
science, Syngenta and Cortevaagrascience, which, you know,
(06:48):
kind of at that time, had justformed. And that was a really
interesting opportunity, becauseit brought together the, there's
a was a big genomics group inIowa with the former DuPont
side. And then, of course, the alot of the herbicide folks on
the former Dow side inIndianapolis. So what the
(07:08):
consortium does is, with thefunding from the companies, and
then corteva, with theirgenomics core in Iowa, they're
actually doing the sequencingthat brought us this place.
Yeah, 2020 and 2021, welaunched, there's matching
funding from the foundation forfood and agriculture research,
and it finally solved thisproblem. Because I think for
years before this, people hadsaid, hey, you know, we want to
(07:31):
do a genome. So, you know, ifyou're at a university, you
write up a grant proposal andyou send it in, and then you get
the comments back. Well, you'venever done a genome. We don't
think you know how to do it, andit's going to take you three
years to get it done, and you'renot gonna be able to do all the
cool work that you want to dowith it. And we're not
interested in just funding agenome. And so that really made
(07:53):
this possible, so that now Ithink currently, there are over
61 genomes in the database. Youcan go to weedgenomics.org and
check out a lot moreinformation. It's where we put
together the species that arethere, their chromosome number,
their genome size. And then youcan link to the data in what's
called weedpedia. That's anothersite, but you just go that you
(08:16):
can it's free to request anaccount, and you can get a
login. They can go in andactually find your favorite weed
and search for your favoritegenes and get all the
information there. And more andmore of those are coming online
as we're getting these genomes,now that they've gone through
the assembly the annotationprocess, where we understand,
(08:36):
you know what, all genes arethere and and everything. And
then, then they're posted. Sothat's been, it's been a great
time. A lot of people involved,and as well, a lot of good
conferences and training alongthe way. I think it's another
part. Is for folks in WeedScience you know are coming
from, maybe from an agronomybackground, chemistry
background, and these genomicstools requires another set of
(08:59):
training and knowledge aboutwhat to do. So we've had some
great meetings, both standaloneand in combination with the WSSA
in the US, the European weedResearch Society, and meeting in
Australia, where we haveopportunities for training. So
also, if somebody wants to getsome basics, maybe on molecular
biology or on how to run an RNASeq experiment, for example, how
(09:24):
to run a blast. We have sometraining videos on the
weedgenomics.org website. Youcan check those out as well.
Joe Ikley (09:30):
So I just had to look it up and user beware when you
search weedpedia. The first linkI came to brought me to a
cannabis repository.
Todd Gaines (09:41):
So it is a hazard of the Weed Science space,
right? Do you ever get theseemails from somebody like, hey,
I want to doing a project. Iwant to talk to somebody in
cannabis and reply back like,well, not that kind of Weed
Science.
Joe Ikley (09:58):
So we'll, we'll link to the Proper weed pedia in the
show notes.
Todd Gaines (10:02):
There we go, perfect.
Alyssa Essman (10:06):
I think that's a really cool example of
universities and industry andeveryone kind of working
together to, you know, generatethese really impactful
resources. One of the things youmentioned was how, you know,
some of these technologies aregoing to influence how we
understand herbicide resistance.And so could we talk a little
(10:27):
bit about how you know this workis allowing us to better
understand the genetic componentof of herbicide resistance?
Todd Gaines (10:36):
Absolutely, because there are cases in herbicide
resistance where a lot isalready known. For example, if
we think of group two alsherbicides, a lot of times, we
can look at the target sitegene. And if you look at a
typical grad student, probably15 to 18 years ago, their whole
(10:59):
PhD would have been cloning andsequencing the ALS gene and
finding that mutation that hadbeen quite an accomplishment and
difficult to do in a new weedspecies, but now we can go into
this database, and you have thesequence at hand for all 30 to
40,000 genes in the species,including ALS, and you can
(11:20):
easily develop the tools,molecular tools, that you need
to go in and sequence it andanalyze it. So it gives us a big
head start, just in the senseof, if we're going after a
target site gene and looking fora target site mutation, really
will help things go faster. Sothat's a that's a nice
advantage. And then we have thecases of mechanisms where we
(11:42):
don't really know what's goingon, and this is still the case
for quite a few things. Forexample, when it comes to
glyphosate, there's somemechanisms that we know about.
We're talking pigweeds. Youknow, they typically have extra
copies of the target site genethat's called epsps, and that
can occur different ways, butthere are quite a few cases
(12:03):
where there's some kind of nontarget site mechanism that we
still just don't really know,actually how that works. Maybe
they they're not translocatingglyphosate as much, but we're
still not the point where wecould say, here is the gene with
its mutation and it causes thatchange in that resistance. So
what can we do now? Because wehave these genomes, we have the
(12:25):
whole map of the DNA. It enablesus to do genetic mapping. And
this is what people in plantbreeding would do when they want
to identify a new diseaseresistance gene, or, you know,
those kind of things. We cantake a resistant and a
susceptible individual, crossthem, and then you self
pollinate that you get an f2 andwhat that does is it kind of
(12:46):
shuffles the genetic deck sothat now you know all these
things that might have beenassociated with resistance, just
through population history,shared ancestry, that kind of
stuff. We can shuffle it all upwith the susceptible, and then
we can use genetic markersacross the whole genome. For
example, Palmer amaranth has 17chromosomes, and the whole
(13:09):
genome is about 450 million basepairs. So you think about that,
that's a lot of information, butwith these advanced sequencing
technologies. Now, by the way, Imeant to mention that if the you
know, the first plant referencegenome cost more than, you know,
the most expensive house in thecountry, essentially, you know,
(13:30):
now you can sequence the genomeof Palmer Amaranth for about the
cost of a Big Mac. So that's agives you a sense of the cost.
Now, you've got to do somethingwith that data once you get it.
But, you know, you can generatemillions and millions of base
pairs of sequence data for, youknow, 10s of dollars. So that's
kind of amazing. So now we canget those genetic markers
(13:52):
across, those 17 chromosomes ofPalmer amaranth, for example,
and find out where does thesequence that comes from the
resistant parent associate withthe resistance trait. So it's
kind of like you almost run anANOVA on each of these markers
and find out which one is isassociated with being resistant.
(14:15):
Now you can zoom in on a regionof the genome to give a few
examples of this. We're workingon a case of 2,4-D resistance in
another conyza horseweed speciesfrom Brazil. And it's a bit
unusual in that the plantsactually have this very rapid
response to 2,4-D they die. Youknow, the cells start when you
(14:37):
see reactive oxygen species andmembrane leakage and everything
within about 15 minutes aftertreating the plant, our mapping
shows that it's probably asingle gene. And what we've done
then is we've made one of thesemapping populations and re
sequenced it, and from the wholegenome of that species, that's
(14:58):
about a billion based Pairs.We've narrowed it down to a
region that's about 20 millionbase pairs. So that's still a
lot. You know, there's stillmaybe 100 genes or so in that
region, but, you know, talkabout sort of making a much
smaller haystack to find yourneedle in, right? You know, the
gene with this mutation has tobe in there somewhere. So that's
(15:20):
making some progress. Similarthings have happened with
Dicamba resistance, for example,in Kochia, you know,
particularly in the West,Dicamba resistance has been an
issue for quite some time.Dicamba is used a lot in the no
till fallow part of the croppingcycle, as well as whenever
you've got corn in the system.So there's been a lot of
(15:41):
selection pressure for Dicambaresistance and Kochia, and we
recently had a project where wedid this as well. We crossed and
resistant by susceptible, mappedit, and we're able to find a
region on the chromosome. Andthen going a bit further, we
found that there's this targetgene. It's one of the CO
receptors for auxin, and it hada mutation. Is an unusual
(16:02):
mutation, and that somethingcalled a transposon had inserted
into the gene. So thesetransposons, you know, might be
familiar with it from corn.Barbara McClintock studied this.
You know, in corn you can getthese, the kernels will have
different colors, right, anddifferent patterns, and that's
due to transposons moving aroundand disrupting the pigment
(16:25):
synthesis genes. And so theirtransposons are really common in
plants, and some of them are notmoving. Some of them do move,
but it just happens as one movedinto that gene, and by doing so,
it changed the sequence right atthe Dicamba binding site, and it
enabled it that then now thatversion of the protein doesn't
(16:46):
bind to Dicamba anymore. So thatwas kind of a really interesting
one, again, that we can map. Andthen, more recently, in palmer
amaranth, working people workingon glufosinate resistance. You
know, people in Arkansas havebeen looking at this for a
little while, and previouslywith Palmer amaranth that was
known that there's this thingcalled an extra chromosomal,
(17:10):
circular DNA. Now, what is that?It's I told you, a Polymer has
17 chromosomes. That's itsnormal genome. But somehow, and
this is something we still needto learn a lot more about, but
this extra circle of DNA hasformed, so kind of think about
it like a very small chromosome,but it's a circle, and it's
(17:32):
about 400,000 base pairs long,and it has roughly 60 coding
genes in it that A lot of themare expressed, and it just
happens that somehow that circleof DNA picked up epsps, the
target gene for glyphosate, andthat then gives it an over
expression, and it makes them,those plants resistant to
(17:53):
glyphosate. That's how that'sgenerally working in Palmer
amaranth. Now, the peoplelooking at glufosinate went back
to that ECC DNA and sequence itagain, and it turns out that the
target gene of glufosinate isnow in their glutamine
synthetase. And so the same waythat the plant has this
mechanism to over express a genenow is also over expressing
(18:13):
glutamine synthetase andsurviving glufosinate. So that's
another case where having thisgenomic information, as well as
the sequencing tools allowedreally fast progress to be made
to figure out, hey, you know,here's what's going on and and
how it's organized. Now, when wethink about some of the big
issues out there, 2,4-D anddicamba resistance in pigweeds,
(18:34):
we don't have a clear picture onthat. It's kind of coming
together. I think a lot ofpeople are working on studying
it, but now these tools areavailable, and we can compare,
for example, a waterhemp genomereference against a resistant
one. People will be able to usethat, maybe to find 2,4-D
Dicamba resistance mechanisms.There is an interesting example
(18:56):
of 2,4-D resistance in waterhempthat comes from before the use
scenario in soybean and cotton.It's from a place in Nebraska
where they're producingbluegrass seed, perennial grass
seed. So they're using 2,4-D foryears to control broad leaves in
that and they selected for areally high level of resistance
(19:19):
to 2,4-D in waterhemp. Turnsout, those plants, rather than
having one of these target sitemutations, they're able to break
down 2,4-D really rapidly, andthey do so through a pathway
that is kind of similar to whatthe grasses do, because grasses
can break down 2,4-D prettyrapidly. So these waterhemp
plants now are able to detoxify2,4-D, very quickly. Again, we
(19:43):
used mapping and the referencegenome of at the time,
originally with a cropamaranthus, the grain amaranth.
But now, you know, we can dothat mapping in the waterhemp
genome itself, and we're able tofind a region that it looks like
there's some some of theseherbicide metabolism genes
there. So still working ontrying to figure out exactly
which one it is. But you know,again, the bottom line is,
(20:06):
there's a similar type oftechnology as what people are
using in human medicine. And youknow, all these areas where
there are a lot ofbreakthroughs, we can now access
that same technology inagriculture and even in Weed
Science, and that lets us studymore complicated things and move
faster and get better answers tohelp us understand what's going
(20:29):
on out there,
Joe Ikley (20:30):
I've got a dumb follow up question. that's what
I'm good for. so question Ioften get asked is, we'll look
at Palmer. So how does thisoverall kind of innocuous weed
from the desert go and spreadacross a whole bunch of the
(20:51):
country and become this plantthat grows very fast, very tall,
very competitive? And I imaginethat someone must be exploring
the pathway of using this typeof technology to maybe look at
some of that. I'm just curiousif that is, if that question has
been asked using this type ofapproach,
Todd Gaines (21:07):
I think that's a huge question, Joe, and it's,
it's fascinating, right? Justthink about that. You know, this
plant that lives in these, youknow, desert ravines and is a
wild plant, you know, one ofmany out there in the desert,
and happens to have thisincredible c4 photosynthesis
(21:28):
capacity that, you know, it'sone thing about Palmer amaranth
that's been measured to have oneof the fastest photosynthesis
rates of any plant out there.It's really efficient. But,
yeah, what happened? How did itemerge from the desert and
become one of our main, youknow, row crop weeds across such
a huge area and continuing toexpand. Because not only, you
know, is it spreading across thenorthern us, as we know, you
(21:50):
know, fairly recently, in placeslike Minnesota and New York and
Michigan, it's becoming aproblem in Spain and Italy and
Turkey and Israel. It's inChina, it's in Japan. It's in
South Africa. Recently spendingsome time in Australia, and
they're gearing up theirmonitoring system because, you
(22:12):
know, that's the only continentthat is not on yet. And so
they're very aware that it's abig problem. They don't want it.
But, yeah, exactly the Why wasthe explanation for this? What
is, are there certain thingsthat have been selected? Is
there something that mutatedand, you know, new kind of
(22:32):
capacity evolved? That'sdefinitely the question people
are asking. I think it's andwith these tools now, it's where
there's there's one area ofgenomics called the pan genome.
So it's kind of like you have areference genome, you know, from
a single individual, but now youcan also get the whole genome of
another individual, and start toask, where does it have does it
(22:56):
have extra copies of certaingenes? Has it lost certain
genes? Are there some of thesetransposons that have moved
around? Is the expression ofcertain genes changing? That's a
big question, and I think thatit's one that people are looking
at, and I feel hopeful that in afew years, we'll start to have
at least some initial answersfor that.
Joe Ikley (23:19):
Thank you.
Alyssa Essman (23:23):
Sounds like, you know, there's a whole range of
information that we're going tobe able to gather, and not only
have deeper understanding, butalso a lot more rapidly than we
were able to before from some ofthis work. So as we were
thinking about this and kind ofdigging into the topic, one of
the really interesting thingsthat popped up was some of this
(23:44):
current work towards creating aspray solution for gene
silencing in weeds. Could youtell us a little bit about that
work and maybe any potential forcontrol?
Todd Gaines (23:59):
Absolutely, this is an area that I am super excited
about, and I'm spending a lot oftime on these days, and other
groups are as well. It's an ideathat's been out there for a
while, but if you kind of stepback a little bit, and just as a
refresher that you know, we'vebeen talking about the genes and
the DNA, that's the instructionmanual. And then the RNA is when
(24:22):
the cells recognize, okay, weneed this gene right now. Let's
turn it on. So the RNA is thiskind of temporary instruction
molecule that goes and thenthat's used to actually make the
protein that goes and does thething, whatever it is the
reaction or the structure in thecell. So the, you know, plant
cells are constantly turningthese genes on and off, and
(24:44):
there's certain RNAs that arearound. Now, when we think about
our main we management toolthat's small molecule
herbicides, nearly every one ofthem is going, you know, you're
got to enter the plant, right?It's either got to pass the
cuticle of the leafAnd get intothe cells, or it's going to come
in through the root with thewater stream and get into the
(25:04):
cells. It'll go in and it'sgoing to bind to some kind of
protein and either inhibit itsreaction or stop it from doing a
structural thing, you know, inthe case of tubulin, something
like that. But they're all asmall molecule that is binding
to a protein, and we're so we'reworking at that protein level.
If we can knock out thatprotein, some of these proteins
(25:26):
are really essential, so losingits function is lethal, or
sometimes knocking it outcreates something that's lethal,
like if we interfere the, youknow, the group five herbicides
that interfere withphotosynthesis, if you block
that, then now we get electronsand free radicals and that kind
of thing. However, now if wetalk about gene silencing, we
(25:48):
switch from trying to target theprotein to targeting that RNA.
So like I said, that RNA isthere, but it's transient and
it's a fairly fragile molecule.So there are a number of ways in
which this can be done. There'sa major pathway that's called
RNAi, which stands for RNAinterference. And this kind of
(26:10):
technology is actually alreadyin the field for insect
management. So there are, thereare things where you can
actually, you can do a transgeneinto the crop genome and make
one of these RNAi molecules.What it is is you basically do
the backwards version of the RNAsequence, and it will
(26:31):
complementary base pair bind toits target, RNA. So he's just,
you know, kind of taking thereverse of it the plant cells
making that so then when itrecognizes that certain RNA, in
this case, say, an insect, youknow, a beetle or a moth larvae,
that's going to be feeding onthe plant, it's going to ingest
that, that RNAi trigger, andit's going to silence that gene
(26:54):
in the insect and control it. Sothose are out there. And also,
there's a company called GreenLight bioscience that this year
has one of these spray on RNAiproducts for, I think it's
Colorado potato beetle. And soagain, you spray it on, you
spray on this double it's calledthe double strand RNA. Normally,
(27:15):
RNA is a single strand, but thisdouble strand is there on the
plant, for example, and theinsect will eat it, and triggers
this gene, silent team pathway,RNAi. So that works for critters
that are chomping on plants,right? But what about weeds
we've got to actually spray iton. So what's the challenge
there? You know, a typical smallmolecule herbicide has, you can
(27:38):
measure the size of a moleculein a unit called Daltons, or
kilo Daltons. So just the togive you a sense that a typical
herbicide is in the range of 30to 40 kilo Daltons, and so
that's that's a size that isable to go into a plant cell and
cross cell walls and go throughthe cuticle and all that stuff.
(28:01):
When we're talking about some ofthese RNA eye triggers or spray
on gene silencing, they might bein the range of 5000 to 10,000
kilodaltons. So they're much,much larger, and they're also
very water soluble, and they'repotentially easily degraded.
Plants have lots of defensesagainst these small RNAs,
(28:22):
because that's typically what aplant virus is going to look
like, is going to they're also,they're the form of a of an RNA.
So plants have lots of enzymesand things that break down,
break down our RNA. So what canwe do about that? You know, we
can figure out how to have abetter formulation. So think,
you know, it really draws on thesame kind of formulation
(28:43):
technology that we use withherbicides. You know, can we
adjust the ratio of thelipophilic component and the
hydrophilic component? Are therethings we can do to spread out
the droplet or or make it have asharper angle, to drive a
concentration gradient? The samekind of questions are the things
we're looking at. So we can put,let's call it a nucleic acid, so
(29:06):
that just is a term for, youknow, a little piece of one of
these RNAi triggers. We can puta tag on that with fluorescent
tags. We could see it under amicroscope. And we'll do
experiments where we might try,you know, maybe a surfactant
that's more has more hydrophiliccomponent, or more lipophilic,
you know, whatever it might be.And then we can look at it, that
(29:29):
leaf under the microscope, andfigure out how much is actually
going into the cuticle, how muchis going into the cells. We can
have markers for the DNA, thenucleus of the cell, and see how
much is getting there, but thatis really, you know, the kind of
research that I've been workingon, and other groups have been
working on, you know, probablyfor about five years now, in
(29:51):
terms of how can we get solvethis problem of getting what is
a very large and delicatemolecule into the plant. But
progress is being made therenow. Talk on the other side of
it, what happens when weactually get it in because we're
going after the RNA? Now,potentially, there's a whole new
playbook or toolkit of thingsthat we can go after, because
(30:13):
herbicides are somewhat limitedby you've got to get find an
effective inhibitor of aprotein. It's got to be a
protein that, if you knock itout, it's lethal. But now we
could go after any RNA we want,as long as we can get this the
it's the chemical properties ofthe of the trigger are
essentially the same no matterwhat Gene we're going after. And
(30:35):
also, now that we have all thesegenomes with all this
information, we can go afterthings that are currently
herbicide targets, but you goafter things that are not, you
know, there's a whole lot ofinformation in Plant Biology
about, if you knock out thisgene, the plant can't live. So,
hey, let's try that. Then Ithink this is where this gets
(30:55):
really fun. So, you know, howcould this be better? Like, you
know? So herbicides work reallywell. We have issues with
resistance. You know, it can bea lot of challenging as far as
the stewardship of thesemolecules and their registration
and all the things that comewith that. So what's better
about gene silencing? For onething, off target effects, by
design, we can really minimizethe risk of that. So because we
(31:19):
design, for example, one ofthese triggers needs to be
they're usually 22 bases long.So you design that so it exactly
matches. For example, the targetpigweed, it doesn't target the
crop. So this as long as it hasto be a perfect match. So if
there are two or three basesthat don't match, it doesn't
affect the crop. It's safe forthe person applying it that you
(31:42):
know will not there's no matchto any RNA in the in the people
who are using it and andinteracting with it, consuming
the product. Later. When youthink of the soil microbiome,
you know, there's no you makesure, we can check it against
all these databases and makesure there's no match there, you
think of off target, maybeendangered species, birds, fish,
(32:05):
amphibians, etc. They can makesure that it's not having any
effect on anything else. Thatcan be very, very precise and
very selective. So, you know, wethink of, we spend a lot of time
thinking about crop safety andbalancing that with weed
management. And this should be,you know, a very precise tool.
Now, with that precision comes abit of a trade off, and that,
(32:28):
you know, there's not going tobe, because you can't have one
trigger that controls all yourbroad leaves and all your
grasses, right? Because they'regoing to have different
sequences. However, I think anice way to think about this is,
you know, when you go you wantto paint room in your house,
right? And you look at all theoptions, and you that's the
favorite color I want. The storedoesn't have all of those colors
(32:49):
mixed up, right? They have thebase colors, and they know how
to mix up that exact one. Well,that's what we could start to
do, is you could go in and say,hey, well, in my field, you
know, I've got palmer amaranth,I've got waterhemp, and I've got
barnyard grass I want to mix forthat, you know, I don't care
about velvetleaf or I don't careabout prickly sida or whatever,
and you get the ones just yourcustom mix for what you need. Go
(33:13):
even a little bit further, youknow, you think of the precision
spray technologies we've gotnow, and can we get to a place
where those are even able toidentify the species you might
actually have, you could have,you know, 10 different of these
gene silencing triggers loadedin the system and the and the
spray is recognizing, okay,that's Palmer amaranth. It draws
(33:34):
that and sprays it, you know.Okay, that's a grass it brings
that one in and sprays it again.You know, maybe that's all
getting a bit complicated, butwith this precision, come will
come the opportunity to dopotentially new things that we
haven't thought about doingbefore as well. There's
resistance, just as we thinkabout it with herbicides. We've
(33:56):
got to think about it in thissense as well, because now you
know of mutation, and this iswhat weeds are good at as
mutations. We'll make it so thatthat one doesn't match anymore.
So how can we monitor that andrespond? Well, if the population
does have a mutation, we candesign another oligo that
matches that form, add it to themix. We can have multiple
(34:18):
targets, maybe that are appliedat once. So maybe you're
targeting three or four geneswith the spray. You could
potentially Think about it likea flu vaccine. You know, every
year the manufacturer comes outwith a different mix of gene
targets. So even as theapplicator, you're not even in a
situation where you could beusing the same thing two years
(34:39):
in a row, because there's enoughoptions. You can always be
mixing it up, combining thatwith now our genomics
understanding and the low costthese tools to monitor for these
mutations that are out there. Ithink, you know, if we can solve
this problem around the deliveryand we've got to figure out, you
know, how does this fit? Howdoes this work? I think that
there's just a. Incredible rangeof of options, of how this could
(35:03):
be applied to make it, you know,a really nice additional partner
and another tool in the toolbox.
Joe Ikley (35:09):
Yeah, I always like to it's easier in my mind to
keep things as simple aspossible. So as you were kind of
going through that, I'mthinking, one of the other
questions I get off are askedquite often, is, is glyphosate
useless? And I'm always like,no, it Yeah, for three or four
key weeds that we have, it, it'sjust about there, but all the
(35:32):
other weeds we have to deal withstill a super effective and
cheap molecule. So yeah, if I'vegot waterhemp and kochia, I can
do my water hemp and kosher RNAblend, and then glyphsate will
take care of the rest. And justone, one of the simple ways of
possibly integrating it, beforewe go down to all the
potentially more complicated andcomplex routes that we could end
(35:53):
up at one day.
Todd Gaines (35:55):
That's right, that's right. It would
definitely partner with with theexisting tools. And yet, you
know, maybe it's a tailoredsolution you have, you know,
here's a really bad resistanceproblem. Let's, let's bring this
in and take care of that, and wethen other things are picking up
the rest of our issues.
Alyssa Essman (36:12):
I was trying to think through some questions
that I think, you know, growersmight have about this
technology. One of what youaddressed, which is the
resistance issue. Do we have anysense of how rapidly resistance
might develop something likethis, relative to herbicides? Is
that somewhat, no, it there.
Todd Gaines (36:32):
There are a couple couple things around that, I
think, if you're just looking atthis particular, you know,
single target site on these 22base pair things, the big
challenge that we know for takePalmer Amaranth as an example, a
plant that makes 100,000 500,000seeds per plant. And you know,
(36:53):
you think of the sheer numbersof that across, you know, the
growing regions where, whereit's an issue. What it means is
essentially every single basepair in that genome has a
mutation, potentially somewherein some individual. So if you
start using this kind oftechnology on that broad sense,
what it's going to reveal veryquickly are the mutant
(37:15):
individuals that have a mismatchin that right. So it is almost
whereas we often can think aboutlike a if, let's say we had a
new herbicide. Theoretically, aresistant mutation is roughly
anywhere in the range of aboutone in 10,000,001 in 20 million.
That's a pretty good guess. Andyou know, how much area does it
(37:39):
take to have 20 million PalmerImran individuals, not that
much, unfortunately, but it's ait doesn't, you know, obviously,
when we start, if we did have anew herbicide, it's not like the
first year you start seeingsurvivors and resistance. But
these, what I'm trying to say isthe potential frequency of
resistance is higher. So I thinkyou need to, right away have a
(38:00):
very sort of proactive andreactive resistance management.
And that's but how we do thatthen is the kind of combination
approach. So if we have, youknow, a target for Gene one and
a target for Gene two, now theprobability of an individual
having mutation to both of thosedrops a lot. If you're bringing
a third one, you get that numbervery, very low. Then, if you're
(38:24):
changing those each year and notputting the selection pressure
on one, that's where you drop itreally low. Now, does that
become practical from amanufacturing and a use
perspective? I think those arequestions and challenges that
have to be addressed. But Ithink that with a there could be
a good design to help reducethat risk of resistance,
(38:47):
although it's still definitelybe a concern, you'd want all the
monitoring and and integrated,you know, non chemical practices
get rid of survivors. All thosesame things would be especially
important.
Joe Ikley (39:03):
I was also thinking through all the different
redundancies that plants have.Of if you silence one thing,
will they find a way to just goahead and survive that year just
because of the redundancy builtinto the survival mechanisms? Or
can't, can't get up, move, sogotta survive somehow?
Todd Gaines (39:21):
Yeah, I think we could be certain that, you know,
if this were to be used andbecame a widely used practice,
we would see plants evolving inways that we go, Oh, I didn't
expect that, you know, there'dbe some kind of surprise, yeah,
could they metabolize thesethings? Maybe they could. Would
they there are these pathwaysthat we're using the cells own
(39:42):
process to do the silencing. Socould they maybe have a mutation
in that such that they don'trecognize this little trigger
anymore? You know? All you know,if we've learned anything from
herbicide resistance, it's justabout anything can be possible.
Yeah.
Alyssa Essman (40:02):
This idea of the really targeted approach,
though, and you know, like youmentioned with vaccines, mixing
it up year to year is reallyexciting. And I think one of the
other questions growers wouldask us, you know, how far away
are we from potentially having atechnology like this available?
Todd Gaines (40:18):
Yeah, it's, you know, it's a great question.
That's probably one of thehardest ones to answer, because
there's a side of me, you know,it's optimistic. I mean, we're
working on this, and there aregroups particularly there. I
know the Brazilian governmenthas this whole initiative on
RNAi tools for pest managementthat they've funded, and there's
a lot of stuff happening. Andthere are startup companies out
(40:41):
there doing this, particularlyin the insect space. I think
that's really driving it along.So you could, you know, if
you're to do a search for RNAicompanies, there are a lot of
them out there. So people arereally working on this. Weeds
are probably the mostchallenging. You know, I'd say
insects the best application.Fungal pathogens have good
(41:01):
applications for this. Thechallenge is to get these gene
silos and triggers into weeds.So how quickly can we solve
that? And then how quickly canthis product come to market? You
know, there are questions onjust how does this look like
from a regulatory perspective?For example, you know, if we
have a given 22 base pairsequence of a given RNAi
(41:23):
trigger, and you change threebase pairs of it, is that a
whole new molecule that needs anew registration package? Or is
that a variant that, you knowcan go under the same safety and
assessment package? You know, Icertainly don't have the answers
to those kind of things, and so,you know, that will be a step in
bringing it to market. Certainlyis the the safety assessment and
(41:46):
regulation. How does that fit inmanufacturing questions? You
know, I think it's a solvableproblem, but it's one of these
things that you can make tons ofthese, of these nucleic acid
triggers. But right now the costof doing that is very high. You
need to, you need to switch to adifferent scale, to different
chemistry, to make them at thatlarge scale. And you wouldn't do
(42:08):
that unless you have a need ormarket for it, right? It's like,
so you can bring the cost of itway down. You need to have a
reason to do so. So howsomebody's gonna have to
navigate that kind of, you know,production and demand divide,
but it's, I think it'stechnically feasible. So let me
just you know, I hope that inthe range of seven to 10 years,
(42:30):
we would could have somethinglike this in the market. I
really do, and I know I'mcertainly getting up every day
and working on this to try to domy part to help make that
happen. And but it'll be a lotof people, and we'll need
breakthroughs in various spacesto get it there.
Alyssa Essman (42:47):
I think it's a really interesting and exciting
space to be in. And I'm curiousto know, how do you envision,
you know, all of these effortstogether, influencing the future
of weed management?
Todd Gaines (42:59):
Well, I think what it can do is give us more tools,
and I think the ability to nowwith resistance, to be able to
respond, you know, when, if wehave a small molecule herbicide
and there's resistance outthere, we can't change that
herbicide and make it now ableto control that resistance,
right? Whereas with this genesilencing technology, we can,
(43:20):
let's say, suddenly, now 90% ofPalmer amaranth has this
different mutant form of ourtarget gene. We can change what
we're synthesizing to target it,if it's you know, through that
pathway. So I think that there'sa way to we can incorporate this
faster information aboutresistance, as well as
resistance to our our regularherbicides to make better
(43:42):
decisions, and maybe even cometo more like a personalized weed
management kind of approach. Youknow that, you know here's what
you've got going on in thisfield, your soil types, your
precipitation patterns, yourcropping goals, the weeds you've
got, what is going to work onthem, what's not and put that
all into your mix, as well aswith these precision
(44:02):
technologies, see and spray kindof things that you can know.
Okay, here's my best option ofthe best weed management at the
least cost and the longestproductivity. So it's really, I
think that the genomic sideallows us to have better
diagnostics. You know, we couldpotentially get to something
(44:23):
where you can walk out in thefield and crush up a leaf and
put it in a little test stripand have an answer, you know, is
it resistant or not? So, youknow, if you're working with the
consultant or the you know,whoever the advisor, you can
make your decision right thenand not say, well, we'll send it
off to a lab, and maybe we'llknow in a month. You know that I
think that we could get to aplace of timely information and
(44:46):
then expand the toolbox so that,again, we just have more
information and we can makebetter choices.
Alyssa Essman (44:55):
So we have one final question for you here that
we've been asking our guests atthe end of the episodes, and
that is, is there a silverbullet for weed control?
Todd Gaines (45:05):
I like this question and thinking about it,
I wanted to come at it from theangle that I'm always thinking
about, which is geneticdiversity. And again, you think
of Palmer amaranth, waterhemp,kochia. These are the kind of
weeds that, when we do so, wecan do something with population
genetics, where we can ask, youknow, you might like all these
(45:28):
pigweeds that are in one field,are they kind of more related to
each other, more similar to eachother at the genetic level, than
they are to pigweed that is 100miles away, 500 miles away? What
do you think is the answer forthat? Let's say Palmer amaranth.
What would you predict?
Joe Ikley (45:49):
depends on how that population got there? I think
about this quite often, wherewe've got some importations
through some contaminated grainscreenings, and I think I've got
some fields that have the entiregenetic diversity of the
Southern Great Plains in onefield.
Todd Gaines (46:06):
Absolutley and I bet you do, because that's what
we find time and again. If youtake two Palmer Amaranth
individuals from the same field,they're pretty much just as
different from each other, asthey are from a Palmer Amaranth
on the other side of thecountry. So even your point,
(46:26):
it's just really hits the nailon the head. If you've got 20
Palmer Amaranth plants there,you have variation, probably
just about every gene in thegenome. And there's a huge
amount of genetic diversity,because they, you know, they
have to outcross, and also thatthere's something in that
question you asked earlierabout, why is this such a
(46:46):
successful weed? That's one ideathat a lot of people are talking
about is, you know, can weedsactually generate more mutations
in their genome, whether throughtransposons, whether through
things like this circular DNA.We are talking about that, even
just a few weeds there, they'vegot a ton of genetic diversity.
So that's why I think my answerwould be, No, there's not a
(47:07):
silver bullet. Because no matterwhat that silver bullet is,
there is some kind of geneticvariant out there that is going
to allow those weeds to escapeit, and it doesn't have to be
resistant to that particular youknow, if it's a chemical control
option, think of weed shifts,right? One of the, I think an
amazing story with Kochia isthat there's this kind of long
(47:30):
term weed management study inwestern Nebraska at Scottsbluff,
and they noticed that Kochia wassurviving in a lot of these
plots that got a group 27 preemergence, early in the season
for years. So they thought,okay, maybe we've got HPPD
resistance here. Got samples ofthose seeds go the greenhouse.
(47:50):
No resistance whatsoever.They're completely sensitive.
However, what was thatpopulation doing? It had shifted
its its germination was delayedabout 30 days after that
herbicide breaks down, right? Soit's just able to escape. So you
know, and that you know, thepopulation that's not its ideal
time to germinate. But is therea variation for that late
(48:11):
germination, even in a 10 by 30foot plot? You bet it's there.
So I think that, you know, nomatter what we do, if we find
something that works reallywell, and we keep doing it over
and over, as weeds will willshift. There's there's variation
out there that is going to comeback and get us
Joe Ikley (48:29):
so. So that silver bullet questions is always my
it's my problem, my brain child,because I, I've often not really
enjoyed being asked thatquestion, because then my my
tongue in cheek response hasjust been silver bullet or for
werewolves, you know, that'severy movie and book I consumed
growing up. But now that I thinkabout I've never read anything
(48:51):
about the genetic diversity ofwerewolves, so never talked
about that,
Todd Gaines (48:56):
right? Is there a werewolf out there somewhere
that says, Yeah, give me all thesilver you've got. Yeah, I grew
up in Colorado, so I thinkabout, you know, your Coors
Light can silver bullet, but
Alyssa Essman (49:12):
Well, thank you Todd for joining us. We want to
give you an opportunity here to,you know, list any, maybe lab
websites or social media siteswhere people can find you or
more information about thistopic. Yeah,
Todd Gaines (49:25):
they can check out weedgenomics.org. That's the
place where we've got the genomeinformation. We have webinars,
and if we're having a conferenceor any training, and if we just
want to learn more about thegenetics of weeds, there's,
there's a lot of informationthere. We also have a review
paper from earlier this year, ifyou're wondering, well, what
would you do with all thesewheat genomes, really? And so we
(49:47):
have this paper that talksabout, kind of all the different
ideas that people have thoughtof and how we can use wheat
genomes. We've mostly talkedabout herbicides today, but can
we look at biology and dormancyand ecology and all these
things? With weeds. And so thatpaper is in a journal called
Genome biology, and JakeMontgomery is the first author.
And I can send you that link forthat paper. It's an open access
(50:10):
one, so anybody can take a lookat it if you really want to dive
into the topic.
Alyssa Essman (50:16):
Well, thank you again for joining us. Thank you
for all of your work on thistopic. I think it's really
fascinating and very importantand very promising. And we thank
the listeners, and we hopeyou'll tune in next week to the
war against weeds podcast.
Thanks for tuning in. Just areminder, you can find this and
(50:37):
other podcasts and resources onthe crop protection network.
This network has a host ofinformation from extension
programs across the US about allthings pest management. We hope
to catch you next week on thewar against weeds. Podcast.
Music.
Alyssa Essman (00:07):
Welcome back to the war against weeds podcast.
This is Alyssa Essman, WeedScience extension specialist at
the Ohio State and today I'mjoined by my co host, Dr Joe
Ikley at North Dakota StateUniversity. How's it going Joe?
Joe Ikley (00:19):
Not too bad, still relatively warm during the days.
So winter isn't here yet.
Alyssa Essman (00:28):
It's coming upon us rather quickly. I fear. Today
we're really excited to bejoined by Dr Todd Gaines,
professor at Colorado StateUniversity, to talk about a
really unique and interestingtopic, and that is, you know,
novel methods for for pigweedcontrol and kind of his area of
expertise. So, Todd, you want totell us a little bit about what
you do at Colorado State.
Todd Gaines (00:50):
Yeah. Hi Alyssa. Hi Joe. Thanks. It's great to chat
with you today. What I work on.I'm really interested in the
genetics of wheat, understandinghow they do what they do, and
why they're so successful, andno matter the very best ideas we
have to get rid of them andmanage them that they're always
seeming to come up with a way torespond and to understand that
(01:13):
from the genetics angle, whetherthat's herbicide resistance,
whether that's shifts Inemergence, you know, how can we
understand from their geneticdiversity background, how weeds
are responding to our managementpractices?
Alyssa Essman (01:29):
Awesome. So that's kind of a good place to
start. We have a question herefirst to kind of help give us
some background and maybe evensome resources. But I was
wondering if you could give ussome information on the
international weed GenomicsConsortium, maybe what it is,
and how you've been involvedwith that.
Todd Gaines (01:47):
Yeah, I'd like to start by going back a little bit
to sort of the start of thegenomics era for plant. You
know, we have the first plantthat had its genome assembled
and put together. So that's, youknow, the genome is the
collection of all the DNA, allthe genes and other structural
(02:07):
parts of the DNA that make up tochromosomes. And, of course,
that contains the instructionsfor how to make the plant. The
first one for the model plant,Arabidopsis. It's a little
mustard that it's kind of a wildplant and northern latitudes
around the world. That genomewas completed in the year 2000
and it's really interesting tothink that, you know,
(02:29):
altogether, that effort, youknow, probably cost somewhere
roughly in the range of tenmillion you know, in terms of
the sequencing and the time. Andit was a many, many year
project, and that genome stillcontinues to be updated, but
it's a really incrediblyvaluable reference for plant
biology, understanding at a verybasic level how plants work. And
(02:51):
then you zoom forward to, youknow, probably in the range of
about 10 years after that, a lotof people are starting to think,
could we do genomes for weedsand genomes for major crops were
getting done. You know, Rice wasdone, corn was done and
appointed there millet andpeople working on tomato and
(03:12):
soybean, wheat was a morechallenging one, a bigger genome
coming later. But certainly, youknow, you could see a lot of
value and reason to invest indoing these crop genomes, and
they were at that pointbecoming, you know, maybe multi
million dollar projects, butless than 10 million. So still,
you know, to do a weed species,very, very expensive. And so
(03:33):
there are a lot ofconversations, particularly at
the Weed Science meetings aroundmaybe, could we pick a model
weed and find the resources tomake that happen, and it really
never, kind of got moved out ofthat. Then we moved into the era
of next generation sequencing,as it's called, and this brought
an incredible drop in the costof getting DNA sequence. So it's
(03:57):
kind of like, you know, justlike the computer processors in
our computers get faster. Theysort of double in capacity about
every 18 months. There's thisthing called Moore's law that
sort of describes that, thatthey're going faster and faster
all the time. And you know that,right? If you have a two year
old computer, suddenly it'slike, why is this so slow, you
know? And you get a new one, andthat's essentially what
(04:19):
happened. There's thisincredible change in the
technology that now we could gethuge amounts of data and the
cost dropped by orders ofmagnitude. So then people could
start to work with the RNA, withthe expressed genes. And so we
can call that the transcriptome.Each RNA is called the
transcript, and those are,again, the instructions for the
(04:39):
genes that make the proteinsthat do everything in the plant.
And that really became feasiblefor weeds in the range of 10 to
12 years ago. And you startseeing people using that to
study herbicide resistance inparticular, start to find new
mutations for resistance forthings like group one you know,
your grass herbicides and. Andsome work was also done on group
(05:02):
four herbicides, the auxins. Butstill, it didn't give us a
picture of the whole genome, youknow, all the other information
in addition to the genes. Soagain, this is going along in
about 2016 there's aninternational Weed Science
meeting in Prague, and there's aworkshop there on weed genomics.
(05:22):
And so a lot of people wherethey're talking and thinking,
Okay, this cost has come down.We have these important weed
species. We see reasons why we'dwant to do this. That was when
people started thinking, howcould we actually make this
happen? And the idea cametogether that a lot of the crop
protection companies, you know,that discover and market
(05:43):
herbicides. They were doing someof this work, and a few of them
had maybe a genome or two, ormaybe some of these
transcriptomes. But of course,they had that information
themselves. They're using it fortheir own projects. And the
thought was, is there a way thatif these companies could come
together and pool some resourcesthat these genomes could get
(06:03):
done and then be shared with thewhole Weed Science community.
And that's that started the ballrolling on these conversations
and more workshops, moremeetings, and it was eventually
by actually in 2020. Was anotherkind of milestone into the first
really complete, well donegenome of what we call a real
(06:25):
weed was done. That washorseweed, can I say, conyza
canadensis, that was done by agroup from mag, Canada. And then
in that same year was when theplan really solidified for the
International weed GenomicsConsortium. So that brought
together the companies,including BASF, Bayer crop
science, Syngenta and Cortevaagrascience, which, you know,
(06:48):
kind of at that time, had justformed. And that was a really
interesting opportunity, becauseit brought together the, there's
a was a big genomics group inIowa with the former DuPont
side. And then, of course, the alot of the herbicide folks on
the former Dow side inIndianapolis. So what the
(07:08):
consortium does is, with thefunding from the companies, and
then corteva, with theirgenomics core in Iowa, they're
actually doing the sequencingthat brought us this place.
Yeah, 2020 and 2021, welaunched, there's matching
funding from the foundation forfood and agriculture research,
and it finally solved thisproblem. Because I think for
years before this, people hadsaid, hey, you know, we want to
(07:31):
do a genome. So, you know, ifyou're at a university, you
write up a grant proposal andyou send it in, and then you get
the comments back. Well, you'venever done a genome. We don't
think you know how to do it, andit's going to take you three
years to get it done, and you'renot gonna be able to do all the
cool work that you want to dowith it. And we're not
interested in just funding agenome. And so that really made
(07:53):
this possible, so that now Ithink currently, there are over
61 genomes in the database. Youcan go to weedgenomics.org and
check out a lot moreinformation. It's where we put
together the species that arethere, their chromosome number,
their genome size. And then youcan link to the data in what's
called weedpedia. That's anothersite, but you just go that you
(08:16):
can it's free to request anaccount, and you can get a
login. They can go in andactually find your favorite weed
and search for your favoritegenes and get all the
information there. And more andmore of those are coming online
as we're getting these genomes,now that they've gone through
the assembly the annotationprocess, where we understand,
(08:36):
you know what, all genes arethere and and everything. And
then, then they're posted. Sothat's been, it's been a great
time. A lot of people involved,and as well, a lot of good
conferences and training alongthe way. I think it's another
part. Is for folks in WeedScience you know are coming
from, maybe from an agronomybackground, chemistry
background, and these genomicstools requires another set of
(08:59):
training and knowledge aboutwhat to do. So we've had some
great meetings, both standaloneand in combination with the WSSA
in the US, the European weedResearch Society, and meeting in
Australia, where we haveopportunities for training. So
also, if somebody wants to getsome basics, maybe on molecular
biology or on how to run an RNASeq experiment, for example, how
(09:24):
to run a blast. We have sometraining videos on the
weedgenomics.org website. Youcan check those out as well.
Joe Ikley (09:30):
So I just had to look it up and user beware when you
search weedpedia. The first linkI came to brought me to a
cannabis repository.
Todd Gaines (09:41):
So it is a hazard of the Weed Science space,
right? Do you ever get theseemails from somebody like, hey,
I want to doing a project. Iwant to talk to somebody in
cannabis and reply back like,well, not that kind of Weed
Science.
Joe Ikley (09:58):
So we'll, we'll link to the Proper weed pedia in the
show notes.
Todd Gaines (10:02):
There we go, perfect.
Alyssa Essman (10:06):
I think that's a really cool example of
universities and industry andeveryone kind of working
together to, you know, generatethese really impactful
resources. One of the things youmentioned was how, you know,
some of these technologies aregoing to influence how we
understand herbicide resistance.And so could we talk a little
(10:27):
bit about how you know this workis allowing us to better
understand the genetic componentof of herbicide resistance?
Todd Gaines (10:36):
Absolutely, because there are cases in herbicide
resistance where a lot isalready known. For example, if
we think of group two alsherbicides, a lot of times, we
can look at the target sitegene. And if you look at a
typical grad student, probably15 to 18 years ago, their whole
(10:59):
PhD would have been cloning andsequencing the ALS gene and
finding that mutation that hadbeen quite an accomplishment and
difficult to do in a new weedspecies, but now we can go into
this database, and you have thesequence at hand for all 30 to
40,000 genes in the species,including ALS, and you can
(11:20):
easily develop the tools,molecular tools, that you need
to go in and sequence it andanalyze it. So it gives us a big
head start, just in the senseof, if we're going after a
target site gene and looking fora target site mutation, really
will help things go faster. Sothat's a that's a nice
advantage. And then we have thecases of mechanisms where we
(11:42):
don't really know what's goingon, and this is still the case
for quite a few things. Forexample, when it comes to
glyphosate, there's somemechanisms that we know about.
We're talking pigweeds. Youknow, they typically have extra
copies of the target site genethat's called epsps, and that
can occur different ways, butthere are quite a few cases
(12:03):
where there's some kind of nontarget site mechanism that we
still just don't really know,actually how that works. Maybe
they they're not translocatingglyphosate as much, but we're
still not the point where wecould say, here is the gene with
its mutation and it causes thatchange in that resistance. So
what can we do now? Because wehave these genomes, we have the
(12:25):
whole map of the DNA. It enablesus to do genetic mapping. And
this is what people in plantbreeding would do when they want
to identify a new diseaseresistance gene, or, you know,
those kind of things. We cantake a resistant and a
susceptible individual, crossthem, and then you self
pollinate that you get an f2 andwhat that does is it kind of
(12:46):
shuffles the genetic deck sothat now you know all these
things that might have beenassociated with resistance, just
through population history,shared ancestry, that kind of
stuff. We can shuffle it all upwith the susceptible, and then
we can use genetic markersacross the whole genome. For
example, Palmer amaranth has 17chromosomes, and the whole
(13:09):
genome is about 450 million basepairs. So you think about that,
that's a lot of information, butwith these advanced sequencing
technologies. Now, by the way, Imeant to mention that if the you
know, the first plant referencegenome cost more than, you know,
the most expensive house in thecountry, essentially, you know,
(13:30):
now you can sequence the genomeof Palmer Amaranth for about the
cost of a Big Mac. So that's agives you a sense of the cost.
Now, you've got to do somethingwith that data once you get it.
But, you know, you can generatemillions and millions of base
pairs of sequence data for, youknow, 10s of dollars. So that's
kind of amazing. So now we canget those genetic markers
(13:52):
across, those 17 chromosomes ofPalmer amaranth, for example,
and find out where does thesequence that comes from the
resistant parent associate withthe resistance trait. So it's
kind of like you almost run anANOVA on each of these markers
and find out which one is isassociated with being resistant.
(14:15):
Now you can zoom in on a regionof the genome to give a few
examples of this. We're workingon a case of 2,4-D resistance in
another conyza horseweed speciesfrom Brazil. And it's a bit
unusual in that the plantsactually have this very rapid
response to 2,4-D they die. Youknow, the cells start when you
(14:37):
see reactive oxygen species andmembrane leakage and everything
within about 15 minutes aftertreating the plant, our mapping
shows that it's probably asingle gene. And what we've done
then is we've made one of thesemapping populations and re
sequenced it, and from the wholegenome of that species, that's
(14:58):
about a billion based Pairs.We've narrowed it down to a
region that's about 20 millionbase pairs. So that's still a
lot. You know, there's stillmaybe 100 genes or so in that
region, but, you know, talkabout sort of making a much
smaller haystack to find yourneedle in, right? You know, the
gene with this mutation has tobe in there somewhere. So that's
(15:20):
making some progress. Similarthings have happened with
Dicamba resistance, for example,in Kochia, you know,
particularly in the West,Dicamba resistance has been an
issue for quite some time.Dicamba is used a lot in the no
till fallow part of the croppingcycle, as well as whenever
you've got corn in the system.So there's been a lot of
(15:41):
selection pressure for Dicambaresistance and Kochia, and we
recently had a project where wedid this as well. We crossed and
resistant by susceptible, mappedit, and we're able to find a
region on the chromosome. Andthen going a bit further, we
found that there's this targetgene. It's one of the CO
receptors for auxin, and it hada mutation. Is an unusual
(16:02):
mutation, and that somethingcalled a transposon had inserted
into the gene. So thesetransposons, you know, might be
familiar with it from corn.Barbara McClintock studied this.
You know, in corn you can getthese, the kernels will have
different colors, right, anddifferent patterns, and that's
due to transposons moving aroundand disrupting the pigment
(16:25):
synthesis genes. And so theirtransposons are really common in
plants, and some of them are notmoving. Some of them do move,
but it just happens as one movedinto that gene, and by doing so,
it changed the sequence right atthe Dicamba binding site, and it
enabled it that then now thatversion of the protein doesn't
(16:46):
bind to Dicamba anymore. So thatwas kind of a really interesting
one, again, that we can map. Andthen, more recently, in palmer
amaranth, working people workingon glufosinate resistance. You
know, people in Arkansas havebeen looking at this for a
little while, and previouslywith Palmer amaranth that was
known that there's this thingcalled an extra chromosomal,
(17:10):
circular DNA. Now, what is that?It's I told you, a Polymer has
17 chromosomes. That's itsnormal genome. But somehow, and
this is something we still needto learn a lot more about, but
this extra circle of DNA hasformed, so kind of think about
it like a very small chromosome,but it's a circle, and it's
(17:32):
about 400,000 base pairs long,and it has roughly 60 coding
genes in it that A lot of themare expressed, and it just
happens that somehow that circleof DNA picked up epsps, the
target gene for glyphosate, andthat then gives it an over
expression, and it makes them,those plants resistant to
(17:53):
glyphosate. That's how that'sgenerally working in Palmer
amaranth. Now, the peoplelooking at glufosinate went back
to that ECC DNA and sequence itagain, and it turns out that the
target gene of glufosinate isnow in their glutamine
synthetase. And so the same waythat the plant has this
mechanism to over express a genenow is also over expressing
(18:13):
glutamine synthetase andsurviving glufosinate. So that's
another case where having thisgenomic information, as well as
the sequencing tools allowedreally fast progress to be made
to figure out, hey, you know,here's what's going on and and
how it's organized. Now, when wethink about some of the big
issues out there, 2,4-D anddicamba resistance in pigweeds,
(18:34):
we don't have a clear picture onthat. It's kind of coming
together. I think a lot ofpeople are working on studying
it, but now these tools areavailable, and we can compare,
for example, a waterhemp genomereference against a resistant
one. People will be able to usethat, maybe to find 2,4-D
Dicamba resistance mechanisms.There is an interesting example
(18:56):
of 2,4-D resistance in waterhempthat comes from before the use
scenario in soybean and cotton.It's from a place in Nebraska
where they're producingbluegrass seed, perennial grass
seed. So they're using 2,4-D foryears to control broad leaves in
that and they selected for areally high level of resistance
(19:19):
to 2,4-D in waterhemp. Turnsout, those plants, rather than
having one of these target sitemutations, they're able to break
down 2,4-D really rapidly, andthey do so through a pathway
that is kind of similar to whatthe grasses do, because grasses
can break down 2,4-D prettyrapidly. So these waterhemp
plants now are able to detoxify2,4-D, very quickly. Again, we
(19:43):
used mapping and the referencegenome of at the time,
originally with a cropamaranthus, the grain amaranth.
But now, you know, we can dothat mapping in the waterhemp
genome itself, and we're able tofind a region that it looks like
there's some some of theseherbicide metabolism genes
there. So still working ontrying to figure out exactly
which one it is. But you know,again, the bottom line is,
(20:06):
there's a similar type oftechnology as what people are
using in human medicine. And youknow, all these areas where
there are a lot ofbreakthroughs, we can now access
that same technology inagriculture and even in Weed
Science, and that lets us studymore complicated things and move
faster and get better answers tohelp us understand what's going
(20:29):
on out there,
Joe Ikley (20:30):
I've got a dumb follow up question. that's what
I'm good for. so question Ioften get asked is, we'll look
at Palmer. So how does thisoverall kind of innocuous weed
from the desert go and spreadacross a whole bunch of the
(20:51):
country and become this plantthat grows very fast, very tall,
very competitive? And I imaginethat someone must be exploring
the pathway of using this typeof technology to maybe look at
some of that. I'm just curiousif that is, if that question has
been asked using this type ofapproach,
Todd Gaines (21:07):
I think that's a huge question, Joe, and it's,
it's fascinating, right? Justthink about that. You know, this
plant that lives in these, youknow, desert ravines and is a
wild plant, you know, one ofmany out there in the desert,
and happens to have thisincredible c4 photosynthesis
(21:28):
capacity that, you know, it'sone thing about Palmer amaranth
that's been measured to have oneof the fastest photosynthesis
rates of any plant out there.It's really efficient. But,
yeah, what happened? How did itemerge from the desert and
become one of our main, youknow, row crop weeds across such
a huge area and continuing toexpand. Because not only, you
know, is it spreading across thenorthern us, as we know, you
(21:50):
know, fairly recently, in placeslike Minnesota and New York and
Michigan, it's becoming aproblem in Spain and Italy and
Turkey and Israel. It's inChina, it's in Japan. It's in
South Africa. Recently spendingsome time in Australia, and
they're gearing up theirmonitoring system because, you
(22:12):
know, that's the only continentthat is not on yet. And so
they're very aware that it's abig problem. They don't want it.
But, yeah, exactly the Why wasthe explanation for this? What
is, are there certain thingsthat have been selected? Is
there something that mutatedand, you know, new kind of
(22:32):
capacity evolved? That'sdefinitely the question people
are asking. I think it's andwith these tools now, it's where
there's there's one area ofgenomics called the pan genome.
So it's kind of like you have areference genome, you know, from
a single individual, but now youcan also get the whole genome of
another individual, and start toask, where does it have does it
(22:56):
have extra copies of certaingenes? Has it lost certain
genes? Are there some of thesetransposons that have moved
around? Is the expression ofcertain genes changing? That's a
big question, and I think thatit's one that people are looking
at, and I feel hopeful that in afew years, we'll start to have
at least some initial answersfor that.
Joe Ikley (23:19):
Thank you.
Alyssa Essman (23:23):
Sounds like, you know, there's a whole range of
information that we're going tobe able to gather, and not only
have deeper understanding, butalso a lot more rapidly than we
were able to before from some ofthis work. So as we were
thinking about this and kind ofdigging into the topic, one of
the really interesting thingsthat popped up was some of this
(23:44):
current work towards creating aspray solution for gene
silencing in weeds. Could youtell us a little bit about that
work and maybe any potential forcontrol?
Todd Gaines (23:59):
Absolutely, this is an area that I am super excited
about, and I'm spending a lot oftime on these days, and other
groups are as well. It's an ideathat's been out there for a
while, but if you kind of stepback a little bit, and just as a
refresher that you know, we'vebeen talking about the genes and
the DNA, that's the instructionmanual. And then the RNA is when
(24:22):
the cells recognize, okay, weneed this gene right now. Let's
turn it on. So the RNA is thiskind of temporary instruction
molecule that goes and thenthat's used to actually make the
protein that goes and does thething, whatever it is the
reaction or the structure in thecell. So the, you know, plant
cells are constantly turningthese genes on and off, and
(24:44):
there's certain RNAs that arearound. Now, when we think about
our main we management toolthat's small molecule
herbicides, nearly every one ofthem is going, you know, you're
got to enter the plant, right?It's either got to pass the
cuticle of the leafAnd get intothe cells, or it's going to come
in through the root with thewater stream and get into the
(25:04):
cells. It'll go in and it'sgoing to bind to some kind of
protein and either inhibit itsreaction or stop it from doing a
structural thing, you know, inthe case of tubulin, something
like that. But they're all asmall molecule that is binding
to a protein, and we're so we'reworking at that protein level.
If we can knock out thatprotein, some of these proteins
(25:26):
are really essential, so losingits function is lethal, or
sometimes knocking it outcreates something that's lethal,
like if we interfere the, youknow, the group five herbicides
that interfere withphotosynthesis, if you block
that, then now we get electronsand free radicals and that kind
of thing. However, now if wetalk about gene silencing, we
(25:48):
switch from trying to target theprotein to targeting that RNA.
So like I said, that RNA isthere, but it's transient and
it's a fairly fragile molecule.So there are a number of ways in
which this can be done. There'sa major pathway that's called
RNAi, which stands for RNAinterference. And this kind of
(26:10):
technology is actually alreadyin the field for insect
management. So there are, thereare things where you can
actually, you can do a transgeneinto the crop genome and make
one of these RNAi molecules.What it is is you basically do
the backwards version of the RNAsequence, and it will
(26:31):
complementary base pair bind toits target, RNA. So he's just,
you know, kind of taking thereverse of it the plant cells
making that so then when itrecognizes that certain RNA, in
this case, say, an insect, youknow, a beetle or a moth larvae,
that's going to be feeding onthe plant, it's going to ingest
that, that RNAi trigger, andit's going to silence that gene
(26:54):
in the insect and control it. Sothose are out there. And also,
there's a company called GreenLight bioscience that this year
has one of these spray on RNAiproducts for, I think it's
Colorado potato beetle. And soagain, you spray it on, you
spray on this double it's calledthe double strand RNA. Normally,
(27:15):
RNA is a single strand, but thisdouble strand is there on the
plant, for example, and theinsect will eat it, and triggers
this gene, silent team pathway,RNAi. So that works for critters
that are chomping on plants,right? But what about weeds
we've got to actually spray iton. So what's the challenge
there? You know, a typical smallmolecule herbicide has, you can
(27:38):
measure the size of a moleculein a unit called Daltons, or
kilo Daltons. So just the togive you a sense that a typical
herbicide is in the range of 30to 40 kilo Daltons, and so
that's that's a size that isable to go into a plant cell and
cross cell walls and go throughthe cuticle and all that stuff.
(28:01):
When we're talking about some ofthese RNA eye triggers or spray
on gene silencing, they might bein the range of 5000 to 10,000
kilodaltons. So they're much,much larger, and they're also
very water soluble, and they'repotentially easily degraded.
Plants have lots of defensesagainst these small RNAs,
(28:22):
because that's typically what aplant virus is going to look
like, is going to they're also,they're the form of a of an RNA.
So plants have lots of enzymesand things that break down,
break down our RNA. So what canwe do about that? You know, we
can figure out how to have abetter formulation. So think,
you know, it really draws on thesame kind of formulation
(28:43):
technology that we use withherbicides. You know, can we
adjust the ratio of thelipophilic component and the
hydrophilic component? Are therethings we can do to spread out
the droplet or or make it have asharper angle, to drive a
concentration gradient? The samekind of questions are the things
we're looking at. So we can put,let's call it a nucleic acid, so
(29:06):
that just is a term for, youknow, a little piece of one of
these RNAi triggers. We can puta tag on that with fluorescent
tags. We could see it under amicroscope. And we'll do
experiments where we might try,you know, maybe a surfactant
that's more has more hydrophiliccomponent, or more lipophilic,
you know, whatever it might be.And then we can look at it, that
(29:29):
leaf under the microscope, andfigure out how much is actually
going into the cuticle, how muchis going into the cells. We can
have markers for the DNA, thenucleus of the cell, and see how
much is getting there, but thatis really, you know, the kind of
research that I've been workingon, and other groups have been
working on, you know, probablyfor about five years now, in
(29:51):
terms of how can we get solvethis problem of getting what is
a very large and delicatemolecule into the plant. But
progress is being made therenow. Talk on the other side of
it, what happens when weactually get it in because we're
going after the RNA? Now,potentially, there's a whole new
playbook or toolkit of thingsthat we can go after, because
(30:13):
herbicides are somewhat limitedby you've got to get find an
effective inhibitor of aprotein. It's got to be a
protein that, if you knock itout, it's lethal. But now we
could go after any RNA we want,as long as we can get this the
it's the chemical properties ofthe of the trigger are
essentially the same no matterwhat Gene we're going after. And
(30:35):
also, now that we have all thesegenomes with all this
information, we can go afterthings that are currently
herbicide targets, but you goafter things that are not, you
know, there's a whole lot ofinformation in Plant Biology
about, if you knock out thisgene, the plant can't live. So,
hey, let's try that. Then Ithink this is where this gets
(30:55):
really fun. So, you know, howcould this be better? Like, you
know? So herbicides work reallywell. We have issues with
resistance. You know, it can bea lot of challenging as far as
the stewardship of thesemolecules and their registration
and all the things that comewith that. So what's better
about gene silencing? For onething, off target effects, by
design, we can really minimizethe risk of that. So because we
(31:19):
design, for example, one ofthese triggers needs to be
they're usually 22 bases long.So you design that so it exactly
matches. For example, the targetpigweed, it doesn't target the
crop. So this as long as it hasto be a perfect match. So if
there are two or three basesthat don't match, it doesn't
affect the crop. It's safe forthe person applying it that you
(31:42):
know will not there's no matchto any RNA in the in the people
who are using it and andinteracting with it, consuming
the product. Later. When youthink of the soil microbiome,
you know, there's no you makesure, we can check it against
all these databases and makesure there's no match there, you
think of off target, maybeendangered species, birds, fish,
(32:05):
amphibians, etc. They can makesure that it's not having any
effect on anything else. Thatcan be very, very precise and
very selective. So, you know, wethink of, we spend a lot of time
thinking about crop safety andbalancing that with weed
management. And this should be,you know, a very precise tool.
Now, with that precision comes abit of a trade off, and that,
(32:28):
you know, there's not going tobe, because you can't have one
trigger that controls all yourbroad leaves and all your
grasses, right? Because they'regoing to have different
sequences. However, I think anice way to think about this is,
you know, when you go you wantto paint room in your house,
right? And you look at all theoptions, and you that's the
favorite color I want. The storedoesn't have all of those colors
(32:49):
mixed up, right? They have thebase colors, and they know how
to mix up that exact one. Well,that's what we could start to
do, is you could go in and say,hey, well, in my field, you
know, I've got palmer amaranth,I've got waterhemp, and I've got
barnyard grass I want to mix forthat, you know, I don't care
about velvetleaf or I don't careabout prickly sida or whatever,
and you get the ones just yourcustom mix for what you need. Go
(33:13):
even a little bit further, youknow, you think of the precision
spray technologies we've gotnow, and can we get to a place
where those are even able toidentify the species you might
actually have, you could have,you know, 10 different of these
gene silencing triggers loadedin the system and the and the
spray is recognizing, okay,that's Palmer amaranth. It draws
(33:34):
that and sprays it, you know.Okay, that's a grass it brings
that one in and sprays it again.You know, maybe that's all
getting a bit complicated, butwith this precision, come will
come the opportunity to dopotentially new things that we
haven't thought about doingbefore as well. There's
resistance, just as we thinkabout it with herbicides. We've
(33:56):
got to think about it in thissense as well, because now you
know of mutation, and this iswhat weeds are good at as
mutations. We'll make it so thatthat one doesn't match anymore.
So how can we monitor that andrespond? Well, if the population
does have a mutation, we candesign another oligo that
matches that form, add it to themix. We can have multiple
(34:18):
targets, maybe that are appliedat once. So maybe you're
targeting three or four geneswith the spray. You could
potentially Think about it likea flu vaccine. You know, every
year the manufacturer comes outwith a different mix of gene
targets. So even as theapplicator, you're not even in a
situation where you could beusing the same thing two years
(34:39):
in a row, because there's enoughoptions. You can always be
mixing it up, combining thatwith now our genomics
understanding and the low costthese tools to monitor for these
mutations that are out there. Ithink, you know, if we can solve
this problem around the deliveryand we've got to figure out, you
know, how does this fit? Howdoes this work? I think that
there's just a. Incredible rangeof of options, of how this could
(35:03):
be applied to make it, you know,a really nice additional partner
and another tool in the toolbox.
Joe Ikley (35:09):
Yeah, I always like to it's easier in my mind to
keep things as simple aspossible. So as you were kind of
going through that, I'mthinking, one of the other
questions I get off are askedquite often, is, is glyphosate
useless? And I'm always like,no, it Yeah, for three or four
key weeds that we have, it, it'sjust about there, but all the
(35:32):
other weeds we have to deal withstill a super effective and
cheap molecule. So yeah, if I'vegot waterhemp and kochia, I can
do my water hemp and kosher RNAblend, and then glyphsate will
take care of the rest. And justone, one of the simple ways of
possibly integrating it, beforewe go down to all the
potentially more complicated andcomplex routes that we could end
(35:53):
up at one day.
Todd Gaines (35:55):
That's right, that's right. It would
definitely partner with with theexisting tools. And yet, you
know, maybe it's a tailoredsolution you have, you know,
here's a really bad resistanceproblem. Let's, let's bring this
in and take care of that, and wethen other things are picking up
the rest of our issues.
Alyssa Essman (36:12):
I was trying to think through some questions
that I think, you know, growersmight have about this
technology. One of what youaddressed, which is the
resistance issue. Do we have anysense of how rapidly resistance
might develop something likethis, relative to herbicides? Is
that somewhat, no, it there.
Todd Gaines (36:32):
There are a couple couple things around that, I
think, if you're just looking atthis particular, you know,
single target site on these 22base pair things, the big
challenge that we know for takePalmer Amaranth as an example, a
plant that makes 100,000 500,000seeds per plant. And you know,
(36:53):
you think of the sheer numbersof that across, you know, the
growing regions where, whereit's an issue. What it means is
essentially every single basepair in that genome has a
mutation, potentially somewherein some individual. So if you
start using this kind oftechnology on that broad sense,
what it's going to reveal veryquickly are the mutant
(37:15):
individuals that have a mismatchin that right. So it is almost
whereas we often can think aboutlike a if, let's say we had a
new herbicide. Theoretically, aresistant mutation is roughly
anywhere in the range of aboutone in 10,000,001 in 20 million.
That's a pretty good guess. Andyou know, how much area does it
(37:39):
take to have 20 million PalmerImran individuals, not that
much, unfortunately, but it's ait doesn't, you know, obviously,
when we start, if we did have anew herbicide, it's not like the
first year you start seeingsurvivors and resistance. But
these, what I'm trying to say isthe potential frequency of
resistance is higher. So I thinkyou need to, right away have a
(38:00):
very sort of proactive andreactive resistance management.
And that's but how we do thatthen is the kind of combination
approach. So if we have, youknow, a target for Gene one and
a target for Gene two, now theprobability of an individual
having mutation to both of thosedrops a lot. If you're bringing
a third one, you get that numbervery, very low. Then, if you're
(38:24):
changing those each year and notputting the selection pressure
on one, that's where you drop itreally low. Now, does that
become practical from amanufacturing and a use
perspective? I think those arequestions and challenges that
have to be addressed. But Ithink that with a there could be
a good design to help reducethat risk of resistance,
(38:47):
although it's still definitelybe a concern, you'd want all the
monitoring and and integrated,you know, non chemical practices
get rid of survivors. All thosesame things would be especially
important.
Joe Ikley (39:03):
I was also thinking through all the different
redundancies that plants have.Of if you silence one thing,
will they find a way to just goahead and survive that year just
because of the redundancy builtinto the survival mechanisms? Or
can't, can't get up, move, sogotta survive somehow?
Todd Gaines (39:21):
Yeah, I think we could be certain that, you know,
if this were to be used andbecame a widely used practice,
we would see plants evolving inways that we go, Oh, I didn't
expect that, you know, there'dbe some kind of surprise, yeah,
could they metabolize thesethings? Maybe they could. Would
they there are these pathwaysthat we're using the cells own
(39:42):
process to do the silencing. Socould they maybe have a mutation
in that such that they don'trecognize this little trigger
anymore? You know? All you know,if we've learned anything from
herbicide resistance, it's justabout anything can be possible.
Yeah.
Alyssa Essman (40:02):
This idea of the really targeted approach,
though, and you know, like youmentioned with vaccines, mixing
it up year to year is reallyexciting. And I think one of the
other questions growers wouldask us, you know, how far away
are we from potentially having atechnology like this available?
Todd Gaines (40:18):
Yeah, it's, you know, it's a great question.
That's probably one of thehardest ones to answer, because
there's a side of me, you know,it's optimistic. I mean, we're
working on this, and there aregroups particularly there. I
know the Brazilian governmenthas this whole initiative on
RNAi tools for pest managementthat they've funded, and there's
a lot of stuff happening. Andthere are startup companies out
(40:41):
there doing this, particularlyin the insect space. I think
that's really driving it along.So you could, you know, if
you're to do a search for RNAicompanies, there are a lot of
them out there. So people arereally working on this. Weeds
are probably the mostchallenging. You know, I'd say
insects the best application.Fungal pathogens have good
(41:01):
applications for this. Thechallenge is to get these gene
silos and triggers into weeds.So how quickly can we solve
that? And then how quickly canthis product come to market? You
know, there are questions onjust how does this look like
from a regulatory perspective?For example, you know, if we
have a given 22 base pairsequence of a given RNAi
(41:23):
trigger, and you change threebase pairs of it, is that a
whole new molecule that needs anew registration package? Or is
that a variant that, you knowcan go under the same safety and
assessment package? You know, Icertainly don't have the answers
to those kind of things, and so,you know, that will be a step in
bringing it to market. Certainlyis the the safety assessment and
(41:46):
regulation. How does that fit inmanufacturing questions? You
know, I think it's a solvableproblem, but it's one of these
things that you can make tons ofthese, of these nucleic acid
triggers. But right now the costof doing that is very high. You
need to, you need to switch to adifferent scale, to different
chemistry, to make them at thatlarge scale. And you wouldn't do
(42:08):
that unless you have a need ormarket for it, right? It's like,
so you can bring the cost of itway down. You need to have a
reason to do so. So howsomebody's gonna have to
navigate that kind of, you know,production and demand divide,
but it's, I think it'stechnically feasible. So let me
just you know, I hope that inthe range of seven to 10 years,
(42:30):
we would could have somethinglike this in the market. I
really do, and I know I'mcertainly getting up every day
and working on this to try to domy part to help make that
happen. And but it'll be a lotof people, and we'll need
breakthroughs in various spacesto get it there.
Alyssa Essman (42:47):
I think it's a really interesting and exciting
space to be in. And I'm curiousto know, how do you envision,
you know, all of these effortstogether, influencing the future
of weed management?
Todd Gaines (42:59):
Well, I think what it can do is give us more tools,
and I think the ability to nowwith resistance, to be able to
respond, you know, when, if wehave a small molecule herbicide
and there's resistance outthere, we can't change that
herbicide and make it now ableto control that resistance,
right? Whereas with this genesilencing technology, we can,
(43:20):
let's say, suddenly, now 90% ofPalmer amaranth has this
different mutant form of ourtarget gene. We can change what
we're synthesizing to target it,if it's you know, through that
pathway. So I think that there'sa way to we can incorporate this
faster information aboutresistance, as well as
resistance to our our regularherbicides to make better
(43:42):
decisions, and maybe even cometo more like a personalized weed
management kind of approach. Youknow that, you know here's what
you've got going on in thisfield, your soil types, your
precipitation patterns, yourcropping goals, the weeds you've
got, what is going to work onthem, what's not and put that
all into your mix, as well aswith these precision
(44:02):
technologies, see and spray kindof things that you can know.
Okay, here's my best option ofthe best weed management at the
least cost and the longestproductivity. So it's really, I
think that the genomic sideallows us to have better
diagnostics. You know, we couldpotentially get to something
(44:23):
where you can walk out in thefield and crush up a leaf and
put it in a little test stripand have an answer, you know, is
it resistant or not? So, youknow, if you're working with the
consultant or the you know,whoever the advisor, you can
make your decision right thenand not say, well, we'll send it
off to a lab, and maybe we'llknow in a month. You know that I
think that we could get to aplace of timely information and
(44:46):
then expand the toolbox so that,again, we just have more
information and we can makebetter choices.
Alyssa Essman (44:55):
So we have one final question for you here that
we've been asking our guests atthe end of the episodes, and
that is, is there a silverbullet for weed control?
Todd Gaines (45:05):
I like this question and thinking about it,
I wanted to come at it from theangle that I'm always thinking
about, which is geneticdiversity. And again, you think
of Palmer amaranth, waterhemp,kochia. These are the kind of
weeds that, when we do so, wecan do something with population
genetics, where we can ask, youknow, you might like all these
(45:28):
pigweeds that are in one field,are they kind of more related to
each other, more similar to eachother at the genetic level, than
they are to pigweed that is 100miles away, 500 miles away? What
do you think is the answer forthat? Let's say Palmer amaranth.
What would you predict?
Joe Ikley (45:49):
depends on how that population got there? I think
about this quite often, wherewe've got some importations
through some contaminated grainscreenings, and I think I've got
some fields that have the entiregenetic diversity of the
Southern Great Plains in onefield.
Todd Gaines (46:06):
Absolutley and I bet you do, because that's what
we find time and again. If youtake two Palmer Amaranth
individuals from the same field,they're pretty much just as
different from each other, asthey are from a Palmer Amaranth
on the other side of thecountry. So even your point,
(46:26):
it's just really hits the nailon the head. If you've got 20
Palmer Amaranth plants there,you have variation, probably
just about every gene in thegenome. And there's a huge
amount of genetic diversity,because they, you know, they
have to outcross, and also thatthere's something in that
question you asked earlierabout, why is this such a
(46:46):
successful weed? That's one ideathat a lot of people are talking
about is, you know, can weedsactually generate more mutations
in their genome, whether throughtransposons, whether through
things like this circular DNA.We are talking about that, even
just a few weeds there, they'vegot a ton of genetic diversity.
So that's why I think my answerwould be, No, there's not a
(47:07):
silver bullet. Because no matterwhat that silver bullet is,
there is some kind of geneticvariant out there that is going
to allow those weeds to escapeit, and it doesn't have to be
resistant to that particular youknow, if it's a chemical control
option, think of weed shifts,right? One of the, I think an
amazing story with Kochia isthat there's this kind of long
(47:30):
term weed management study inwestern Nebraska at Scottsbluff,
and they noticed that Kochia wassurviving in a lot of these
plots that got a group 27 preemergence, early in the season
for years. So they thought,okay, maybe we've got HPPD
resistance here. Got samples ofthose seeds go the greenhouse.
(47:50):
No resistance whatsoever.They're completely sensitive.
However, what was thatpopulation doing? It had shifted
its its germination was delayedabout 30 days after that
herbicide breaks down, right? Soit's just able to escape. So you
know, and that you know, thepopulation that's not its ideal
time to germinate. But is therea variation for that late
(48:11):
germination, even in a 10 by 30foot plot? You bet it's there.
So I think that, you know, nomatter what we do, if we find
something that works reallywell, and we keep doing it over
and over, as weeds will willshift. There's there's variation
out there that is going to comeback and get us
Joe Ikley (48:29):
so. So that silver bullet questions is always my
it's my problem, my brain child,because I, I've often not really
enjoyed being asked thatquestion, because then my my
tongue in cheek response hasjust been silver bullet or for
werewolves, you know, that'severy movie and book I consumed
growing up. But now that I thinkabout I've never read anything
(48:51):
about the genetic diversity ofwerewolves, so never talked
about that,
Todd Gaines (48:56):
right? Is there a werewolf out there somewhere
that says, Yeah, give me all thesilver you've got. Yeah, I grew
up in Colorado, so I thinkabout, you know, your Coors
Light can silver bullet, but
Alyssa Essman (49:12):
Well, thank you Todd for joining us. We want to
give you an opportunity here to,you know, list any, maybe lab
websites or social media siteswhere people can find you or
more information about thistopic. Yeah,
Todd Gaines (49:25):
they can check out weedgenomics.org. That's the
place where we've got the genomeinformation. We have webinars,
and if we're having a conferenceor any training, and if we just
want to learn more about thegenetics of weeds, there's,
there's a lot of informationthere. We also have a review
paper from earlier this year, ifyou're wondering, well, what
would you do with all thesewheat genomes, really? And so we
(49:47):
have this paper that talksabout, kind of all the different
ideas that people have thoughtof and how we can use wheat
genomes. We've mostly talkedabout herbicides today, but can
we look at biology and dormancyand ecology and all these
things? With weeds. And so thatpaper is in a journal called
Genome biology, and JakeMontgomery is the first author.
And I can send you that link forthat paper. It's an open access
(50:10):
one, so anybody can take a lookat it if you really want to dive
into the topic.
Alyssa Essman (50:16):
Well, thank you again for joining us. Thank you
for all of your work on thistopic. I think it's really
fascinating and very importantand very promising. And we thank
the listeners, and we hopeyou'll tune in next week to the
war against weeds podcast.
Thanks for tuning in. Just areminder, you can find this and
(50:37):
other podcasts and resources onthe crop protection network.
This network has a host ofinformation from extension
programs across the US about allthings pest management. We hope
to catch you next week on thewar against weeds. Podcast.
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