Episode Transcript
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Mara-Jean Tilley (00:02):
Imagine being able to explore the fascinating world of individual
cells and their genomic makeup, to unravel the mysteries hidden
within our cells and to uncover the intricate mechanisms that
cause disease. Today we meet a cellular genomic scientist working
on cutting edge research that's improving the effectiveness of personalised therapy. Hi,
(00:27):
I'm Mara-Jean Tilley. And this is Medical Minds, the podcast
of the Garvan Institute of Medical Research. In this series,
we're diving deep into the minds of our amazing researchers
to find out how they tick and how they are
working to make our lives better. With me here is
Professor Joseph Powell, Director of Cellular Science at Garvan and
(00:50):
Director of the UNSW Cellular Genomics Futures Institute. Welcome, Joseph.
Joseph Powell (00:56):
Thanks Mara-Jean. Great to be here.
Mara-Jean Tilley (00:59):
Joseph, we've chatted with many of your colleagues at Garvan
about genomics. Before we get into your expertise in cellular genomics,
can you just recap for us why genomics is so important?
Joseph Powell (01:12):
So genomics is a field of research that studies the
way in which DNA and the products of DNA differ
between individuals, and the reason why it's important is if
you think about the way in which we all look differently.
We're different heights. We have different diseases or conditions or
(01:34):
risks of developing different diseases. A major component of that
is due to the differences in genomics between people. So
genomic research and genomic medical research is studying where in
your genome, where in your DNA are the positions that
contribute to diseases and, specifically, how we can use that
(01:57):
information to develop, for example, early screening studies, preventative health
care and probably most importantly, how we can use that
information to develop new therapeutics.
Mara-Jean Tilley (02:11):
And you work in cellular genomics? What is that?
Joseph Powell (02:15):
So cellular genomics is, as the name suggests, the study
of genomics, but at the level or the resolution of
individual cells. And this has been driven by a phenomenal
technological revolution over the last 10 years, but really picking
up over the last five or six years, where technology
(02:37):
has been developed that allows us to generate genomic information
incredibly accurately and at incredible scale at the level of
individual cells. So we can now generate, for example, genomic
information for a single patient's cancer sample for tens or
hundreds of thousands of cells within a single tumour, and
(03:00):
do that in a very rapid and efficient turnaround time.
Mara-Jean Tilley (03:05):
And why is it so important to study individual single cells,
for example, in a cancer patient?
Joseph Powell (03:12):
The reason it's important is that every disease starts at
the level of an individual cell. Cancer is one of
the best examples of this. Cancer starts with a single
mutation or group of mutations in one cell. By the
time a patient visits their doctor and it's detected, in
that tumour, there can be hundreds of different cancer cell types,
(03:33):
each with their own genomic profiles and each of which
will respond to therapies in different ways. Now the reason
why it's really important to study cancers at cell level
and other diseases is that many therapies that we have
today are incredibly effective at treating some of those cancer cells,
and they can kill those cancer cells, and they can
(03:54):
lead to remission. But they have no effect on the
other cancer cells, and so generating a complete profile of
all of the different cells and the genomic profiles of
those different cells allows us to do two things. One,
it allows us to guide personalised therapy. So, for example,
(04:15):
combination therapies that target the different groups of cells within
that that patient. And it also allows us to discover
what is happening in unique cell populations that we can
then develop new therapies for.
Mara-Jean Tilley (04:29):
We've discussed cancer. But how is cellular genomics important when
studying other diseases?
Joseph Powell (04:37):
So the principles that I outlined in cancer apply to
almost every other disease and condition. If you think about
something like autoimmune disease, so another group of conditions and
diseases that are prevalent, widespread and impact a lot of individuals.
Autoimmune diseases arise when your own immune cells attack your body.
(05:01):
But it's not all of your immune cells attacking all
cells in your body. It's one or two very specific
cell subtypes of immune cells that are attacking one or
two very specific other cells in your body. And the
other very interesting component to this is that you can
not only have different cell subtypes that are causing that disease,
(05:24):
but you have differences in the DNA that is driving
that change in different cells. And so, by understanding the
genomic variation at the level of individual cells, we will
be able to guide the most effective therapies for a
patient and longer term, develop new therapies that will not
(05:45):
just treat the symptoms of disease but provide a cure
for the disease.
Mara-Jean Tilley (05:50):
Joseph, can you tell us about the work and research
that you and your team are doing with cellular genomics?
Joseph Powell (05:56):
My team's mission is to develop the next generation of
genomic-led therapies, and we are doing so for a wide
range of different diseases and conditions, everything from autoimmune disease,
cardiovascular disorders and neurological disorders such as Parkinson's and Alzheimer's.
(06:19):
To do this, we generate some of the world's largest
resources of cellular genomics information and data on tens of
thousands of individuals and apply machine learning techniques to identify
the subtle genomic differences between individual cells and how they
(06:39):
are becoming disrupted to cause diseases. By doing this, we
can do two things. Firstly, we can provide precision diagnostic
tests to improve current treatments' outcomes. So, in other words,
improving the efficacy of drugs that are currently offered to patients.
(07:00):
Longer term, we focus on identifying the targets, which can
then be modulated by the latest wave of RNA therapeutics.
Mara-Jean Tilley (07:11):
Let's talk about stem cells because stem cells play a
key role in your research. Why is that?
Joseph Powell (07:19):
Yeah, so we're incredibly excited by the use of stem
cells for our research. I think it's important to make
it clear that we work in an area of stem
cells called induced pluripotent stem cells. So this is a
technology that was developed about 15 years ago. It was
awarded the Nobel Prize 12 years ago, where you can
(07:39):
take a patient's blood sample and reprogram their blood cells
to make what's referred to as a stem cell. And
a stem cell is a cell that has the potential
to make any other cell in the human body. And
that's what pluripotent means. Using pluripotent stem cells we can
then guide those cells to become other cells in the
(08:02):
human body. For example, we can make beating cardiac muscle
cells in the dish. We can create neural organoids, which
we refer to as mini brains, and we can do
this from a patient's own blood sample, which contains their
genetic profile. So when we're trying to understand the way
(08:22):
in which genetic differences contribute to disease and the way
in which you might guide a therapy for a patient
starting with their own genetic material becomes invaluable. Go back
to what I was talking about earlier, about the way
in which disease arises at the level of an individual cell.
If you're trying to study Parkinson's disease, it's obviously very
difficult to get brain cells from patients with Parkinson's disease
(08:46):
for obvious reasons. And so we can use stem cells
to recreate the same cells and the same cell states
for patients with Parkinson's disease, healthy controls. And then we
can use cellular genomic technology to identify what are the
differences between the diseased cell types and the healthy cell types.
(09:08):
Moving forward we can then apply CRISPR technology to correct
for those mutations and return the diseased cell states back
into a healthy cell state. The ultimate outcome of this
will be, one, the development of new therapies like I've described,
but also possibly the application of stem cell transplants back
(09:33):
into a patient. And there are already clinical trials happening
across the world that are doing exactly that.
Mara-Jean Tilley (09:40):
So how long will it be before we see cellular
genomics used more broadly in clinical practice?
Joseph Powell (09:48):
So, genomics has already made an enormous impact in clinical practice.
It's used for, uh, detection of cancers. It's used for
early screening. It's used to design and guide the best therapies.
But to date, all of the genomic technology that is
in clinical practice is what we refer to as bulk genomics.
It's generating data over millions of cells and using a
(10:09):
kind of average signal of those cells to inform the
best treatment outcome. Cellular genomics is already now at the
stage of being translated into clinical practice to improve in
almost all of these application spaces, and it basically will
provide a far greater degree of accuracy and resolution at
(10:31):
guiding therapies, guiding treatment choices and early stage screening for diseases.
So an example of this is our work in Crohn's disease,
where we've been able to show that patients will respond
to different therapies better or worse, depending on their genetic profile.
We're demonstrating this for clinical trials at the moment, running
(10:52):
across a wide range of hospitals in New South Wales
with the aim of developing a simple test that when
a new patient goes to their doctor, they can have
a cheap, simple, fast test to be able to inform
the best therapy to treat their disease.
Mara-Jean Tilley (11:10):
How critical is the development of technology for your research?
Joseph Powell (11:16):
The work that we do and many other researchers at
Govan relies heavily on technology. It's critical, and it's important
that we remain continually at the forefront of where the
technology is being developed and that can be technology in
single cell sequencing. It can be the latest artificial intelligence
or machine learning algorithms, some of which we develop. Or
(11:38):
it can be driving our own stem cell research and
the types of technology that are necessary there. We're at
a very fortunate point because in the last number of
years there's been an incredible rate of technological development across
a number of domains in artificial intelligence and machine learning
algorithms and stem cell technology and ideas. And, of course,
(12:00):
in cellular genomics. And one of the most critical things
for myself and my research team and other labs at
the Garvan Institute is to continually stay at the forefront of
that technology. But we also need to really focus and
think deeply about the types of questions and the clinical
applications of those questions, and the way in which I
(12:22):
think about this is it's really the intersection of these
different approaches, and these different technologies and ideas that allows
us to make the most rapid advances in medical research
and advance the rate in which we're able to improve
health care and ultimately develop new therapies.
Mara-Jean Tilley (12:39):
Can you talk to us more about how you use
machine learning in your research?
Joseph Powell (12:45):
So machine learning is a sub-field of artificial intelligence, and
the way in which we apply it is to develop
algorithms that are then run on enormous – the world's largest –
data sets of their type to help us identify where
in the genome mutations are contributing to disease. And if
(13:06):
we're developing a new therapy, what is the best target
for that therapy in a cell and in a genome?
So the field's advanced to a point now that without
the use of machine learning or artificial intelligence techniques, it
would be impossible to be able to understand and identify
the genomic differences between people that are causing diseases. And
(13:27):
it would certainly be impossible to do it at scale
and scale is completely necessary because of the amount of
diversity between individuals.
Mara-Jean Tilley (13:38):
What do you think the future looks like for medical
research and medicine? What changes can we expect over the
next few decades?
Joseph Powell (13:46):
So I think we're at a particularly exciting moment in
time in medical research. The advances in technology and the
rate in which new ideas can be translated into a
clinical setting, uh has become more rapid and so we're
able to see translation of research in a much shorter
time frame than was previously possible. Where I see the
(14:08):
field going is realistically in the next sort of five to
10 years. I think we will be much, much better
at early diagnosis and early detection of diseases. And that's
critically important because in most instances then those diseases can
be quite treatable and the impact on a patient and
(14:28):
the impact on society more broadly becomes less. Moving forward
into sort of 20 or 30 years. I would place
a confident bet on the fact that we will have
new therapies that provide a cure for the majority of diseases.
Mara-Jean Tilley (14:43):
So does this mean we'll all be living longer?
Joseph Powell (14:46):
So the advances that have been made in medical research
will almost undoubtedly extend human life. But I think more importantly,
they will reduce the amount of suffering and ill health
that a patient or an individual has across their life.
So it allows us really to live healthier, happier lives
(15:06):
for longer.
Mara-Jean Tilley (15:08):
What excites you most about your research?
Joseph Powell (15:11):
There's two things that really excite me about my research.
The first is working with really dedicated, phenomenal, smart people.
It's an absolute joy and a privilege. Outside of that
the thing that really motivates me is is doing something
that's of value for society and doing something that's gonna
make an impact. People that know me well know that
(15:32):
I'm almost pathologically driven by wanting to have outcomes and
wanting to see progress made. That's what really motivates me.
Mara-Jean Tilley (15:40):
Joseph, did you always want to be a scientist?
Joseph Powell (15:43):
No. Is the short answer! I think when I was young,
I didn't know what I wanted to be. And I
think it's only really through having experiences and having opportunities
that you end up finding a path that provides your
own sense of satisfaction and your own sense of self worth,
but also something where you feel that you can make
a contribution to the society more broadly.
Mara-Jean Tilley (16:04):
Joseph. It's time for the fast five. This is where
we find out a little more on what makes you tick.
What do you do in your downtime?
Joseph Powell (16:13):
Well, Mara-Jean, I have a young son and a wife
with a demanding job. So downtime is a subjective concept
to me. But if I had any downtime, I would
mostly be doing outdoor sports, sea kayaking, mountain biking, cycling.
Mara-Jean Tilley (16:26):
What's one of the most challenging things you've ever done?
Joseph Powell (16:30):
So I completed the first solo expedition up the Taman
Negara river system in Borneo when I was about 21
spending about three months travelling up the river system by
dugout canoe, staying with Iban tribespeople, it was pretty wild.
Mara-Jean Tilley (16:46):
Do you have a secret skill?
Joseph Powell (16:48):
I think I'm very good at cooking. Is that a skill? I think
it is.
Mara-Jean Tilley (16:51):
And do you have a signature dish?
Joseph Powell (16:53):
The dish I'm probably most proud of, my son likes
the most, which is Korean beef, which I cook almost weekly.
Mara-Jean Tilley (16:59):
What are you currently reading?
Joseph Powell (17:01):
I'm reading the book. The book How I Built This
is based on a podcast series of the same name
hosted by Guy Raz. And it's interviews and discussions with
founders of companies and in particular focusing on their journeys
and how they learn to become leaders of their particular
fields but also build something that was valuable for society.
Mara-Jean Tilley (17:21):
Is there anything you're afraid of?
Joseph Powell (17:24):
Yeah, I'm absolutely terrified of sharks. I know people should
be terrified of sharks because they're dangerous. But I've had
a couple of unpleasant encounters, and it is a deep
fear of mine that prohibits me doing things that I
would like to do.
Mara-Jean Tilley (17:36):
Go on. What are what are these encounters?
Joseph Powell (17:39):
So I once had an encounter with a great white
shark while sea kayaking, which was a near miss. It
wasn't being super aggressive, but was scary enough when it
came up to my boat. I've had encounters with bull
sharks in the Sydney Harbour or Brisbane River, and when
I was much younger, it wasn't a shark. But I
swam into a whale carcass, which led to a sort
of fear of large fish or animals in water.
Mara-Jean Tilley (18:05):
Thank you so much, Joseph. It's been such a pleasure.
Joseph Powell (18:08):
Thanks, Mara Jean, it's been really great to be here
and talk to you.
Mara-Jean Tilley (18:12):
If you'd like to know more about Professor Joseph Powell's
research or the work we do at the Garvan, head to
Garvan dot org dot au. And if you've enjoyed this podcast,
please leave a review and share with other podcast lovers.
I'm Mara-Jean Tilley. Thanks for listening.
(18:32):
This podcast was recorded on the traditional Country of the
Gadigal people of the Eora Nation. We recognise their continuing
connection to land, waters and community. We pay our respect
to Aboriginal and Torres Strait Islander cultures and Elders past,
present and emerging.