February 20, 2025 • 9 mins
This week on BioTech Nation, Dr. Daniel Kraft explores the discovery of "dark" proteins, thousands of previously unknown proteins in the human body. Scientists believe these hidden proteins could be the key to detecting diseases earlier and developing new treatments.
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Episode Transcript
Available transcripts are automatically generated. Complete accuracy is not guaranteed.
Dr. Moira Gunn (00:11):
We have thousands of proteins, and we're
not even sure what they all do.In fact, we've actually learned
there are even more. Tech NationHealth Chief Correspondent
doctor Daniel Kraft fills us inon the latest in proteomics.
Daniel, welcome back.
Dr. Daniel Kraft (00:29):
Great to be with you.
Dr. Moira Gunn (00:30):
Alright. Now let's talk about something. It's
a word that every so often kindaflies by my head one way or
another. I read it. It's calledproteomics.
Spell it for everybody. What isit and why is it important?
Dr. Daniel Kraft (00:45):
Well, the proteome or proteomics, p r o t
e o m I c s, proteomics, is sortof the emerging study or the the
large scale study of proteins.Right? Proteins are the building
blocks of our living organisms.Right? They when you put them
all together, make ourselves,make our organs, make us whole
organisms.
And understanding the proteinsand the proteome and the picture
(01:08):
of the proteome, particularlythose that are floating around
in your blood, is becoming areally increasingly valuable way
to understand someone's health,to predict diseases before they
happen, to sort of analyze adisease and categorize it, and
providing new potential targetsfor personalized medicine and
tailored health care that'sgonna really, I think, really
(01:28):
shift the future of medicine inpretty exciting ways.
Dr. Moira Gunn (01:30):
Well, I think what's one of the things that's
important about what you justsaid is that, hey, they're the
targets of this precisionmedicine. Why are proteins
floating around in our bodies?Lots of proteins there, hundreds
of thousands of proteins. Whyare they the targets of
precision medicine?
Dr. Daniel Kraft (01:50):
Well, we're all familiar with hopefully
getting to the doctor at leastonce a year and often having our
standard, blood chemistriesdone. And today, you know, you
measure your your sodium, yourpotassium, your creatinine, and
a few proteins like albumin inyour blood, which might give you
an indication of how well yourkidney is working or your or
your liver is working, I shouldsay. But in reality, there's
(02:11):
thousands, you know, ten, twentythousand, different proteins
that are moving through yourblood that can be starting to be
analyzed. There's companies likeSomaLogic and Thermo Fisher that
can measure up to 11,000proteins in just like two
microliters, two one thousandthsof a a milliliter. So, it's it's
an interesting time now to beable to look at those and at
(02:33):
still a bit expensive, maybe$500 per individual, but that's
gonna get cheaper and cheaper.
And what's magic about that, sowhen you can look at several
thousand proteins, we can seewhat's the protein picture of
health, what's the proteinpicture of disease, and what's
happening in between. And we'restarting to understand what
those proteins sort ofsignatures are. You don't need
to measure all ten, eleventhousand or more. You can start
(02:53):
to see we know that these 12proteins change in early
Parkinson's or neurolog otherneurology diseases or early
forms of of cancer. And what'sbeen exciting particularly over
the last couple years,particularly out of work out of
the UK Biobank, so out of UnitedKingdom, they've been measuring
the proteome as well as themedical history of thousands of
(03:14):
Britons.
And now when the data sciencefolks are starting to understand
that, analyze those, and findsome pretty amazing, findings
through sort of proteomicanalysis to the point where
measuring three, four thousandparticipants and looking at
their proteomics is enabling youto predict, I think it's up to
67 diseases from multiplemyeloma to motor neuron
(03:34):
diseases, to pulmonary fibrosis,to heart disease, sometimes
months and years before theymight show up.
Dr. Moira Gunn (03:40):
What you know, what you're really talking about
here is so often we don't evenlook at what's wrong until we
can tell on the outside thatthere is a problem. And even
when it's on the inside, it'slike, it's actually a pretty big
problem already. So we'retalking about really winding
back to the early days. Youknow, we talk stage one, stage
(04:03):
two. These are like stage minusfour, stage minus ten.
Dr. Daniel Kraft (04:07):
I call it, you know, stage zero. And
particularly as we putmultiomics together, your
protein, your proteome, yourgenome, your metabolomics, your
sociom, and sort of integratethat, this idea of the digital
twin we've talked about in priorepisodes, it's gonna really
start to shift how we practicemedicine. Because today, a lot
of medicine is sort of one sizefits all. Moyer, you're my
(04:27):
patient. We'll start to give youyour colonoscopy at the average
age, assuming there's no geneticor family history.
We'll sort of treat you with thesame dose of a statin as
everybody else. But now that youmight have proteomic data,
genomic information, we'll startto predict what's really the
time you might need to bescreened. And by finding
diseases or signs of disease atearly stages, that's the time to
(04:47):
intervene and move you back tosort of your baseline rather
than, as you mentioned, stagethree or stage four disease,
whether that's neurologicdisease, an autoimmune disease,
a cancer. That's where thepromise of proteomics is gonna
be more and more exciting,particularly as it might become
part of our annual exam orsomething you might even do
every month.
Dr. Moira Gunn (05:04):
you this. I'm not exactly sure how many
proteins I have.
Dr. Moira Gun (05:10):
How many different proteins? How many?
I'm like, I'm not exactly sure.
Dr. Moira Gunn (05:16):
How many proteins does a human have? And
if we know and what do we knowabout them? And, you know, are
we actually just studying themnow? What are we doing?
Dr. Daniel Kraft (05:28):
Yeah. So it's been just over twenty something
years since we had the firsthuman genome sequenced. And as
most of the listeners know, yoursort of genes get transcribed
into RNA and, like, those madeinto proteins. And earlier on,
it was thought that maybe weonly had about 30,000 genes that
turned it about 30,000 proteinsthat operated the body. And,
(05:49):
some tallies have lowered thatto only about 20,000 proteins,
which is pretty extraordinary.
But some new evidence recentlypublished in science and other
great journals is, showingevidence of something called the
dark proteome that that suggeststhat we've been missing
thousands of non traditionalgenes, genes that, are encoded a
bit differently than than theold old understood methods. And
(06:11):
that means we're making a wholenew set of proteins often sort
of smaller proteins, some withonly maybe 12 amino acids that
are sort of the basic buildingbox of proteins. So these now
are often called non canonical,proteins are really set to maybe
open up a whole new era ofmedicine. So for example,
there's a pediatricneuroendocrinologist at
University of Michigan calledJohn Pressner who's discovered
(06:34):
some of these new, dark proteoand proteins that seem to play a
key role in a form of braincancer called, medulloblastoma.
And that these littlemicroproteins are sort of
essential for the cancer to toto grow and cause disease.
So that might mean we have newtargets, new drug targets that
can target those particularproteins that might help with
brain cancers and other cancers.So I think, we're opening up a
(06:57):
really interesting new era, andit's gonna be more proteins than
we thought we had.
Dr. Moira Gunn (07:02):
Okay. So we got dark proteins. We got dark DNA.
Dr. Moira Gun (07:08):
I'm like and every single one of these new
ones, they show up, and it'slike, oh, we found it. But we
don't know anything about it. Wedon't know how it relates to
anything. I mean, there's justso much work ahead.
Dr. Daniel Kraft (07:21):
Right. Because, again, today, we pick
up such a small amount of ourdata. Right? That chem twenty or
chem forty only picks up four 40different chemistries from your
blood, a few of which are areproteins. But now that we're
under this age of hopefully lowcost democratized proteomics,
we'll end up again being able tocharacterize someone because the
proteome changes from day to dayto minute to minute.
(07:41):
Your genome stays the sameessentially. But now we'll have
potentially new targets. Somaybe these new mini proteins
will give us new drugdevelopment targets. We'll we'll
get understand new biomarkers ofaging. There's sort of aging
clocks that seem to be proteinsthat are, released by certain
organs from your kidney to yourliver to your heart that can
give us insight.
To not just your sort ofphysiologic age, but the age of
(08:03):
every different organ. We'reseeing a whole new suite of
tools to sort of predict anddetect early cancer, and that's
often done using sometimes DNAand methylation of DNA. But when
you combine proteomics andgenomics information from the
blood, that's gonna be exciting.As we try and do the basics,
optimize your sleep, yourexercise, your social
connection, your mobility, allthose things are gonna be
(08:26):
impacting your proteome, and wecan start to measure those. And
so all these sort ofinterventions across health care
can be measured in new ways, andwe can deliver new insights and
new specific, tools forunderstanding health and
disease.
Dr. Moira Gunn (08:39):
Well, Daniel, may the proteins be with you.
Dr. Daniel Kraft (08:41):
See you next time.
Dr. Moira Gunn (08:43):
TechNation Health chief correspondent,
doctor Daniel Kraft, is thefounder and chair of TechNation
Health on the web at TechnationHealth and digital.health. More
information about Daniel atDanielCraftMD.net.
We have thousands of proteins, and we're
not even sure what they all do.In fact, we've actually learned
there are even more. Tech NationHealth Chief Correspondent
doctor Daniel Kraft fills us inon the latest in proteomics.
Daniel, welcome back.
Dr. Daniel Kraft (00:29):
Great to be with you.
Dr. Moira Gunn (00:30):
Alright. Now let's talk about something. It's
a word that every so often kindaflies by my head one way or
another. I read it. It's calledproteomics.
Spell it for everybody. What isit and why is it important?
Dr. Daniel Kraft (00:45):
Well, the proteome or proteomics, p r o t
e o m I c s, proteomics, is sortof the emerging study or the the
large scale study of proteins.Right? Proteins are the building
blocks of our living organisms.Right? They when you put them
all together, make ourselves,make our organs, make us whole
organisms.
And understanding the proteinsand the proteome and the picture
(01:08):
of the proteome, particularlythose that are floating around
in your blood, is becoming areally increasingly valuable way
to understand someone's health,to predict diseases before they
happen, to sort of analyze adisease and categorize it, and
providing new potential targetsfor personalized medicine and
tailored health care that'sgonna really, I think, really
(01:28):
shift the future of medicine inpretty exciting ways.
Dr. Moira Gunn (01:30):
Well, I think what's one of the things that's
important about what you justsaid is that, hey, they're the
targets of this precisionmedicine. Why are proteins
floating around in our bodies?Lots of proteins there, hundreds
of thousands of proteins. Whyare they the targets of
precision medicine?
Dr. Daniel Kraft (01:50):
Well, we're all familiar with hopefully
getting to the doctor at leastonce a year and often having our
standard, blood chemistriesdone. And today, you know, you
measure your your sodium, yourpotassium, your creatinine, and
a few proteins like albumin inyour blood, which might give you
an indication of how well yourkidney is working or your or
your liver is working, I shouldsay. But in reality, there's
(02:11):
thousands, you know, ten, twentythousand, different proteins
that are moving through yourblood that can be starting to be
analyzed. There's companies likeSomaLogic and Thermo Fisher that
can measure up to 11,000proteins in just like two
microliters, two one thousandthsof a a milliliter. So, it's it's
an interesting time now to beable to look at those and at
(02:33):
still a bit expensive, maybe$500 per individual, but that's
gonna get cheaper and cheaper.
And what's magic about that, sowhen you can look at several
thousand proteins, we can seewhat's the protein picture of
health, what's the proteinpicture of disease, and what's
happening in between. And we'restarting to understand what
those proteins sort ofsignatures are. You don't need
to measure all ten, eleventhousand or more. You can start
(02:53):
to see we know that these 12proteins change in early
Parkinson's or neurolog otherneurology diseases or early
forms of of cancer. And what'sbeen exciting particularly over
the last couple years,particularly out of work out of
the UK Biobank, so out of UnitedKingdom, they've been measuring
the proteome as well as themedical history of thousands of
(03:14):
Britons.
And now when the data sciencefolks are starting to understand
that, analyze those, and findsome pretty amazing, findings
through sort of proteomicanalysis to the point where
measuring three, four thousandparticipants and looking at
their proteomics is enabling youto predict, I think it's up to
67 diseases from multiplemyeloma to motor neuron
(03:34):
diseases, to pulmonary fibrosis,to heart disease, sometimes
months and years before theymight show up.
Dr. Moira Gunn (03:40):
What you know, what you're really talking about
here is so often we don't evenlook at what's wrong until we
can tell on the outside thatthere is a problem. And even
when it's on the inside, it'slike, it's actually a pretty big
problem already. So we'retalking about really winding
back to the early days. Youknow, we talk stage one, stage
(04:03):
two. These are like stage minusfour, stage minus ten.
Dr. Daniel Kraft (04:07):
I call it, you know, stage zero. And
particularly as we putmultiomics together, your
protein, your proteome, yourgenome, your metabolomics, your
sociom, and sort of integratethat, this idea of the digital
twin we've talked about in priorepisodes, it's gonna really
start to shift how we practicemedicine. Because today, a lot
of medicine is sort of one sizefits all. Moyer, you're my
(04:27):
patient. We'll start to give youyour colonoscopy at the average
age, assuming there's no geneticor family history.
We'll sort of treat you with thesame dose of a statin as
everybody else. But now that youmight have proteomic data,
genomic information, we'll startto predict what's really the
time you might need to bescreened. And by finding
diseases or signs of disease atearly stages, that's the time to
(04:47):
intervene and move you back tosort of your baseline rather
than, as you mentioned, stagethree or stage four disease,
whether that's neurologicdisease, an autoimmune disease,
a cancer. That's where thepromise of proteomics is gonna
be more and more exciting,particularly as it might become
part of our annual exam orsomething you might even do
every month.
Dr. Moira Gunn (05:04):
you this. I'm not exactly sure how many
proteins I have.
Dr. Moira Gun (05:10):
How many different proteins? How many?
I'm like, I'm not exactly sure.
Dr. Moira Gunn (05:16):
How many proteins does a human have? And
if we know and what do we knowabout them? And, you know, are
we actually just studying themnow? What are we doing?
Dr. Daniel Kraft (05:28):
Yeah. So it's been just over twenty something
years since we had the firsthuman genome sequenced. And as
most of the listeners know, yoursort of genes get transcribed
into RNA and, like, those madeinto proteins. And earlier on,
it was thought that maybe weonly had about 30,000 genes that
turned it about 30,000 proteinsthat operated the body. And,
(05:49):
some tallies have lowered thatto only about 20,000 proteins,
which is pretty extraordinary.
But some new evidence recentlypublished in science and other
great journals is, showingevidence of something called the
dark proteome that that suggeststhat we've been missing
thousands of non traditionalgenes, genes that, are encoded a
bit differently than than theold old understood methods. And
(06:11):
that means we're making a wholenew set of proteins often sort
of smaller proteins, some withonly maybe 12 amino acids that
are sort of the basic buildingbox of proteins. So these now
are often called non canonical,proteins are really set to maybe
open up a whole new era ofmedicine. So for example,
there's a pediatricneuroendocrinologist at
University of Michigan calledJohn Pressner who's discovered
(06:34):
some of these new, dark proteoand proteins that seem to play a
key role in a form of braincancer called, medulloblastoma.
And that these littlemicroproteins are sort of
essential for the cancer to toto grow and cause disease.
So that might mean we have newtargets, new drug targets that
can target those particularproteins that might help with
brain cancers and other cancers.So I think, we're opening up a
(06:57):
really interesting new era, andit's gonna be more proteins than
we thought we had.
Dr. Moira Gunn (07:02):
Okay. So we got dark proteins. We got dark DNA.
Dr. Moira Gun (07:08):
I'm like and every single one of these new
ones, they show up, and it'slike, oh, we found it. But we
don't know anything about it. Wedon't know how it relates to
anything. I mean, there's justso much work ahead.
Dr. Daniel Kraft (07:21):
Right. Because, again, today, we pick
up such a small amount of ourdata. Right? That chem twenty or
chem forty only picks up four 40different chemistries from your
blood, a few of which are areproteins. But now that we're
under this age of hopefully lowcost democratized proteomics,
we'll end up again being able tocharacterize someone because the
proteome changes from day to dayto minute to minute.
(07:41):
Your genome stays the sameessentially. But now we'll have
potentially new targets. Somaybe these new mini proteins
will give us new drugdevelopment targets. We'll we'll
get understand new biomarkers ofaging. There's sort of aging
clocks that seem to be proteinsthat are, released by certain
organs from your kidney to yourliver to your heart that can
give us insight.
To not just your sort ofphysiologic age, but the age of
(08:03):
every different organ. We'reseeing a whole new suite of
tools to sort of predict anddetect early cancer, and that's
often done using sometimes DNAand methylation of DNA. But when
you combine proteomics andgenomics information from the
blood, that's gonna be exciting.As we try and do the basics,
optimize your sleep, yourexercise, your social
connection, your mobility, allthose things are gonna be
(08:26):
impacting your proteome, and wecan start to measure those. And
so all these sort ofinterventions across health care
can be measured in new ways, andwe can deliver new insights and
new specific, tools forunderstanding health and
disease.
Dr. Moira Gunn (08:39):
Well, Daniel, may the proteins be with you.
Dr. Daniel Kraft (08:41):
See you next time.
Dr. Moira Gunn (08:43):
TechNation Health chief correspondent,
doctor Daniel Kraft, is thefounder and chair of TechNation
Health on the web at TechnationHealth and digital.health. More
information about Daniel atDanielCraftMD.net.
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