October 4, 2024 • 22 mins
More than 33,000 people in Australia today are affected by multiple sclerosis, a disabling disease of the brain and spinal cord, for which there is no cure. In this episode, you’ll meet Dr Seyhan Yazar and Professor Tri Phan who are working to better manage, treat and prevent MS, by investigating what could be a critical link between this disease and a very common virus, the Epstein-Barr Virus.
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Episode Transcript
Available transcripts are automatically generated. Complete accuracy is not guaranteed.
Dr Viviane Richter (00:01):
Imagine this. You're feeling more tired than usual. Your vision
feels off. Your fingers have been tingling for a few days.
For some, these symptoms could mean nothing. But for more
than 33,000 people in Australia, these kinds of symptoms are
the first signs of multiple sclerosis, a disabling disease of
(00:21):
the brain and spinal cord for which there is no cure. Today,
you'll meet two Garvan researchers who are working to better manage,
treat and prevent MS by investigating what could be a
critical link between this disease and a very common virus.
You're listening to Medical Minds, the podcast that takes you
(00:41):
inside the labs at the Garvan Institute of Medical Research.
I'm your host, Dr Viviane Richter, and with me here are
Professor Tri Phan and Dr Seyhan Yazar, who are part of
the Open Coast-to-Coast Australian Multiple Sclerosis consortium. Welcome, Tri and Seyhan.
Professor Tri Phan (00:59):
Hi, Viv. It's great to see you.
Dr Seyhan Yazar (01:00):
Hi, Viv. How are you doing?
Dr Viviane Richter (01:02):
Tri and Seyhan, before we talk about your research on MS
and how this virus fits in, why is there no
cure for MS, a disease that's been around for a
long time?
Professor Tri Phan (01:14):
Look, I think that's a really great question. I think
one of the real challenges of studying a disease like
MS is that everything is happening behind the scenes in
the dark. MS is a disease that affects the brain,
the spinal cord, the optic nerve. These are really difficult
to get at tissues to biopsy, and for those reasons,
we don't know exactly what's going on in there. And
(01:36):
for a long time, people have tried to use surrogate
markers that might tell you that there's inflammation going on
in the brain. So, for example, they've taken fluid from
the spinal cord. It's called cerebrospinal fluid, or CSF, and
you can detect biomarkers of immune activity in the brain.
And then the development of imaging like magnetic resonance imaging,
(01:58):
or MRI technology, has been really great because now we
can see these inflammatory lesions in the brain as they happen.
But that hasn't progressed us to a point where we
understand what is actually going on deep inside these lesions,
what's happening in terms of how the immune system is
being triggered and how the immune system is being activated
(02:19):
to start targeting and destroying parts of ourselves. And I
think the real advance has been, in the last couple
of decades, the understanding of the immune system and the
central role that it plays and the technologies that have
come along that have allowed us, even though we can't get
into these tissues, we can certainly now get to places
where we know immune activation occurs and start tracking these
(02:41):
cells at a single cell resolution that's going to allow
us to tell us what this cell is reacting to, and
why is it being triggered to react in that way?
Dr Viviane Richter (02:50):
What is the prognosis currently for patients?
Professor Tri Phan (02:52):
At the moment, one of the things that's really clear
is that MS has can run multiple different courses. And of course,
for a long time we've had clinical classifications based on
how it progresses. For some people, they have a relapse,
repeating course and other individuals, they may have a progressive course
where they have more and more attacks. And with each attack,
(03:14):
there's damage to the nervous system and they accrue more
and more disability. So what we're hoping moving forward is
develop an understanding that allows us to actually have a
better way to classify these individuals with MS, perhaps at a
molecular level. That might give us some insights into what
their future trajectory might hold, because that will really help
(03:35):
inform us in terms of what we can do in
the present to prevent that future.
Dr Viviane Richter (03:41):
Do we know why MS predominantly affects women and is
often diagnosed in young people?
Professor Tri Phan (03:47):
That is a really great question. And this sexual dimorphism
in terms of how men and women respond differently to
the environment, is something that's increasingly a source of great
interest because it goes to the core of how the
immune system works. That's a long way of saying we
don't know. And, in fact, that is one of the
(04:10):
big research questions that we want to address with the
OCCAMS research program.
Dr Viviane Richter (04:15):
Seyhan, can you paint us a bit of a picture of
where we're at with MS in terms of treatments and diagnostics?
Dr Seyhan Yazar (04:23):
So unfortunately there is no cure, I'll start by saying
that. But we have lots of therapies targeting and helping patients
to relieve them from their symptoms, and some of them
are actually helping to their immune system to fight and
the others like reducing some like inflammation in the body.
(04:45):
But MS itself is not a lethal disease, actually, but
the complications you get with MS can reduce an individual's
life expectancy 5 to 10 years compared to a normal person.
But the new treatments and the current therapies that we
have actually closing that gap greatly.
Dr Viviane Richter (05:05):
How is MS currently diagnosed?
Dr Seyhan Yazar (05:08):
So usually like patients visit their neurologist, and the neurologist does
like MRI scan, where they actually identify lesions. And if
those lesions are multiple and in certain regions of the
body of the brain, the patients are diagnosed with MS.
But that's the time that patients are actually have symptoms.
That's when the disease are already like made damage to
(05:31):
the brain. But prior to that time in the background,
there is some inflammation going on, and this is actually
a great opportunity for us to do some research to
identify individuals like early on rather than becoming symptomatic.
Professor Tri Phan (05:47):
Yeah, I think what Seyhan is describing here is a really
exciting opportunity. I think the goal for all of us
would be to actually to stop MS, and to do that,
we need to be diagnosing or predicting individuals who develop
MS before they've actually accrued any neurological damage. Because the
state of that right now is that we can't reverse
that damage. So our best bet is to stop it
(06:09):
from happening before it does.
Dr Viviane Richter (06:11):
So what does the virus have to do with all
of this?
Professor Tri Phan (06:14):
I think for a long time, because people really didn't
understand what the clues were that they were being told
from individuals with MS, we knew that there was a
strong genetic component. But the genetics doesn't explain all of it.
So that implies that there was a very strong environmental
driver of the development of MS. And, of course, one
(06:34):
of the most obvious things to propose then would be
maybe some sort of virus in the environment that we
didn't really know about. And, over the years, many viruses
have been proposed to be the culprit. The flavour of
the month, I guess, is this virus called the Epstein-Barr virus,
or EBV. This is a virus that many of your
(06:54):
listeners will be familiar with because it causes glandular fever,
or kissing disease, as it's also known as. This is
a virus that infects up to 95% of adults. And
so it becomes then really difficult, if so many people
get infected with it but so few people develop MS, what's
the connection? How do we tease apart the role of
(07:16):
the immune response to the virus and how that then
leads on to development of MS? And that's really the
sort of research that I think people like Seyhan are
really well placed to answer those questions.
Dr Viviane Richter (07:29):
What is the evidence to point to this virus?
Dr Seyhan Yazar (07:32):
Actually, there is a study that was done by the
US Defence Force. And that is the actual the most,
I think, clear evidence of showing that the Epstein-Barr virus is like
involved in MS. And so what they did in this
study is they have looked at their recruits since their start,
(07:54):
and they collected blood samples over years, many years. I
think the youngest like was like 15 years old at
the time of first study. And then, of course, they
came to an age of 45 when they were actually
diagnosed with with any kind of conditions, including MS. That
study gave us the actual causal relationship that we were
(08:18):
previously suspected. Like many, many years. We don't know like,
if it's actually causing the disease directly, or it's like involved,
like in a pathway that is causing another change, which
is like eventually resulting, like in MS. So that is
something that we are like trying to figure out in
the OCCAMS consortium by focusing on how especially the genes
(08:42):
within our body interact with the virus. And so what
is this changing in the body? What type of changes
it does so it can result in MS?
Dr Viviane Richter (08:52):
So how are you tackling this research question?
Dr Seyhan Yazar (08:55):
So, at the moment, we are recruiting MS patients. We
have already collected samples from healthy individuals. We designed a
study and we are waiting to complete our recruitment process.
Once we have all the samples that we have biobanked,
then we will look at different groups within our cohort.
(09:16):
And then we will compare these individuals and we will
do this at the single cell level. Look at the
individual immune cells within the body. We will look at
the gene expression. It involves a lot of like computational work,
which I am the expert, and that's how I'm like actually
involved in the OCCAMS study. What we will do is once
(09:36):
we have the data, we will use supercomputers to do
our analysis. What we are like hoping to achieve at
the end is to find some markers, some key signatures,
so we can then take these and look at how
they are involved by doing some laboratory experiments and validate
(09:57):
this in animal models, perhaps. And then that will allow
us to take this further for drug development or other,
like neurotherapies.
Dr Viviane Richter (10:08):
Tri, when did you first discover that working with Seyhan could
be beneficial for your research?
Professor Tri Phan (10:13):
So, I first heard Seyhan present her work at a
clinical translation school up in Brisbane a couple of years ago,
and she was talking about Onek1K. And I remember being
blown away by, not just what she'd done, but the
clarity with which she'd done it. To me, until then,
(10:34):
this whole thing about genetics and genomics and how DNA
influences RNA, it crystallised at that point, and she was
able to explain it in a way that a non-genetic
person like myself could actually understand then how your genetic
makeup can influence the expression of genes in an individual
(10:54):
cell that might play a key role in a disease process.
Dr Viviane Richter (10:59):
You established the OCCAMS consortium. Can you tell us what
it is and how that will tackle MS?
Professor Tri Phan (11:06):
I might start by saying I didn't really establish OCCAMS.
OCCAMS is one of those things where everyone put their
hand up. I just happened to be the conduit that
made it happen. The Open Coast-to-Coast Australian Multiple Sclerosis Consortium, or OCCAMS, really came
about from a conversation I had with Dr Jennifer Massey,
(11:29):
who is this incredible neurologist across the road from the
Garvan at St Vincent's Hospital. She is, in my mind, one
of the most knowledgeable person about multiple sclerosis, incredibly insightful,
and the conversation basically went along the lines of
all this amazing research going on at the Garvan, and we're
(11:50):
seeing all these people with MS in the clinic. Wouldn't
it be great if we could do something about learning
more about the disease and how we can help these
people and their families?" And so, out of that conversation,
we started thinking about what are the key assets, how
we can mobilise them, and how can we deploy them
in a way that would be really clinically meaningful in
(12:13):
terms of the questions that we tackle. And so, of course,
having recently heard Seyhan present, it was a no-brainer to
think that, actually, a central part of our research program
would then revolve around how we can use the sort
of tools that Seyhan developed in her research with Joseph
Powell to then help us answer the questions that we
(12:36):
wanted to ask about MS. And I think OCCAMS is
really exciting because we were able to mobilise experts in neurology, immunology, genetics,
expert clinicians who are expert in looking after people with MS,
and scientists who have been studying autoimmune diseases across the
(12:58):
country and actually across the world, because we have in
our consortium experts in the UK, in Germany and in
the United States. So I think, really, when you have
a difficult problem like MS, it's gonna take a lot
of different ways of thinking. And I think one of
the great joys that I have in research is being
(13:21):
able to sit in a room with incredibly bright people
who know so many things that I haven't even dreamt of,
and just sitting back and watching them brainstorm and work
out ways. They may not come up with a solution,
but you sit there and you realise if a solution
is going to come, it's going to come from the
people in this room.
Dr Viviane Richter (13:40):
How close are we to eradicating this disease?
Professor Tri Phan (13:43):
My hope is, potentially for some people far fetched, but
I really do think we are now at a crossroads
where all the ingredients are there for us to potentially
maybe stop MS before it happens. So the dream I
think that we all share is the idea that maybe
(14:04):
one day we'll be able to eradicate MS, in the
same way we've been able to eradicate smallpox, by mobilising
the power of the immune system.
Dr Viviane Richter (14:13):
And Seyhan, how hopeful are you that your research will
have a lasting impact for MS patients?
Dr Seyhan Yazar (14:19):
Of course, we cannot change our genetics. That's what we
are born with. But we are aware of what environmental like
factors that we can be exposed to, and our hope
is to be able to diagnose individuals who are likely
to become MS patients before their actual diagnosis. There is
(14:39):
actually a very great interest in this type of research
at the moment. There is a period called MS prodrome,
where someone has some symptoms. But these symptoms are very common,
like fatigue, headache or some urinary tract infections, which is
(15:00):
very common for people normally healthy to have. But those
symptoms are also occurring in MS patients. So, at the moment,
we are trying to identify these key events in someone's
life by monitoring them way before actually they become MS patients.
(15:21):
So one approach that we are doing is we are
collaborating with Liverpool Hospital researchers, where we are looking at
their medical health records and seeing what type of problems
and presentations patient had prior to their diagnosis of MS.
Our hope is to identify key symptoms that could lead
(15:47):
us to understand when MS diagnosis like is happening. What
we'd also like to do is, not only use this
like the information that we get from the electronical medical records,
but also from their blood samples to see if we
can see these early signatures within the blood. But this
(16:09):
is one of the long term goal of OCCAMS consortium
because doing a research and doing it on a disease
like MS will take lots of years. So for a
medical research to actually come with a conclusion, come with
like some treatments, actually takes almost like 20 years. But
(16:29):
we are very hopeful, and we are very excited that
we are at the beginning of this work. And we
have a great team, older like researchers, as Tri has like mentioned,
that are capable with lots of different skills and expertise.
By bringing everyone together, applying these new technologies and approaches,
including artificial intelligence, we are hoping to like come up
(16:53):
with some model or like some prediction of who's going
to become more likely to become or have MS in
the future. And once we do that, then it will
be very easy for us to actually stop and eradicate MS.
Dr Viviane Richter (17:09):
Why is Garvan the place for you to be doing
this research?
Professor Tri Phan (17:12):
I would say Garvan is a really exciting place to
work at, especially now, because we have this seamless integration
between the institute and St Vincent's Hospital next door. So
that dialogue between clinicians and scientists is really, really important
because it really grounds the research and makes sure that
(17:33):
we're asking really important, clinically meaningful questions. But beyond that,
within the Garvan itself, we have some really brilliant minds,
really creative people who are thinking differently. And along with
that comes some really amazing cutting edge technologies that really
(17:53):
allow us, as Seyhan has described, to be able to tease apart,
at the single cell level, the molecular footprints that might
tell us how a cell has been exposed to environment.
And then how it's changed itself in such a way
that now it's become a cell that actually is attacking
the central nervous system. And I don't think there are
(18:15):
many other places in the world that would have all
those things in one place.
Dr Viviane Richter (18:22):
Seyhan, we can hear the enthusiasm in your voice for
this research. What motivates you day to day?
Dr Seyhan Yazar (18:29):
Well, I guess my love of science. I have to
mention that first. But I think being in the clinic,
seeing patients, seeing patients with genetic disorders that sometimes that
you cannot change is really affected me. I think I
am feeling grateful. The work that I will do will
(18:50):
contribute a little bit to the potential treatments and maybe
featuring some cure that might be possible that can actually
change their life.
Dr Viviane Richter (19:04):
We look forward to hearing the outcomes of this incredibly
promising research. Now, before you go, we'd like to get
to know you a little bit better. This section is
called the Fast Five. What was your first job?
Dr Seyhan Yazar (19:18):
I was a tutor and I was teaching year five
and six students. It was fun. They really didn't want
to do a lot of maths. So it was a
bit challenging, but at the end, I think they were grateful.
Professor Tri Phan (19:32):
My first job. OK, so that would have been after school.
I was a kitchen hand in the Queen Victoria building,
making deep pan pizzas and washing dishes.
Dr Viviane Richter (19:43):
Look how far you've come.
Professor Tri Phan (19:44):
I'm still washing dishes.
Dr Viviane Richter (19:47):
Do you have a favourite movie?
Dr Seyhan Yazar (19:49):
I think A Beautiful Mind was my favourite movie. It came out,
I think, it was at high school. And when I
learned the story of the Professor, I was like, really intrigued.
So it really touched me. It's still, I think, remains
as my favourite movie.
Dr Viviane Richter (20:10):
Do you have any secret skills?
Dr Seyhan Yazar (20:12):
No secret, but I love cooking and my family and
friends really enjoy when I cook. I do too, so
they really enjoy when I make lots of Turkish dishes.
Their favourite being this dish called, very traditional, called beans
with rice, which is very traditional, very simple dish. But
(20:32):
it's really warming, especially during winter days.
Dr Viviane Richter (20:36):
Something that's on your bucket list?
Professor Tri Phan (20:38):
A long time ago, I had this idea that I
wanted to climb the north face of El Capitan. I'm
in no condition to climb it now, so definitely that
would now qualify as a impossible bucket list thing to do.
Dr Viviane Richter (20:51):
Do you have a favourite quote or life motto that
resonates with you most?
Professor Tri Phan (20:56):
"Everything's connected" from Dirk Gently's Holistic Detective Agency. Because I think,
at the end of the day, a lot of what
we do in science is trying to draw connections together.
The challenge, though, is and one of the great pitfalls
is that the human mind is very capable of seeing
connections where they don't exist, and that is where we
can fall.
Dr Viviane Richter (21:17):
Seyhan, how about you?
Dr Seyhan Yazar (21:18):
"When one door closes, another will open". It's really easy
to be trapped with pessimism. When you're a scientist, when
you're what do you want to achieve? You are not
there to achieve it yet, or you don't have what
you need to have to achieve it. And so you have
to remain optimistic. And that's the optimism that we need
(21:41):
to pass to our patients as well, that there will
be a hope for them in the future.
Dr Viviane Richter (21:47):
Professor Tri Phan, Dr Seyhan Yazar, thank you so much for
joining us on Medical Minds.
Dr Seyhan Yazar (21:53):
Thanks for having us, Viv.
Professor Tri Phan (21:55):
Thank you, Viv. It's always a pleasure.
Dr Viviane Richter (21:57):
If you'd like to know more about this research or
donate to the work we do at Garvan, head to garvan.org.au.
And if you've enjoyed this podcast, please leave a review
and share with other podcast lovers. I'm Dr Viviane Richter.
Thanks for listening. This podcast was recorded on the traditional
(22:18):
Country of the Gadigal people of the Eora Nation. We
recognise their continuing connection to land, waters and community. We
pay our respects to Aboriginal and Torres Strait Islander cultures
and Elders past, present and emerging.
Imagine this. You're feeling more tired than usual. Your vision
feels off. Your fingers have been tingling for a few days.
For some, these symptoms could mean nothing. But for more
than 33,000 people in Australia, these kinds of symptoms are
the first signs of multiple sclerosis, a disabling disease of
(00:21):
the brain and spinal cord for which there is no cure. Today,
you'll meet two Garvan researchers who are working to better manage,
treat and prevent MS by investigating what could be a
critical link between this disease and a very common virus.
You're listening to Medical Minds, the podcast that takes you
(00:41):
inside the labs at the Garvan Institute of Medical Research.
I'm your host, Dr Viviane Richter, and with me here are
Professor Tri Phan and Dr Seyhan Yazar, who are part of
the Open Coast-to-Coast Australian Multiple Sclerosis consortium. Welcome, Tri and Seyhan.
Professor Tri Phan (00:59):
Hi, Viv. It's great to see you.
Dr Seyhan Yazar (01:00):
Hi, Viv. How are you doing?
Dr Viviane Richter (01:02):
Tri and Seyhan, before we talk about your research on MS
and how this virus fits in, why is there no
cure for MS, a disease that's been around for a
long time?
Professor Tri Phan (01:14):
Look, I think that's a really great question. I think
one of the real challenges of studying a disease like
MS is that everything is happening behind the scenes in
the dark. MS is a disease that affects the brain,
the spinal cord, the optic nerve. These are really difficult
to get at tissues to biopsy, and for those reasons,
we don't know exactly what's going on in there. And
(01:36):
for a long time, people have tried to use surrogate
markers that might tell you that there's inflammation going on
in the brain. So, for example, they've taken fluid from
the spinal cord. It's called cerebrospinal fluid, or CSF, and
you can detect biomarkers of immune activity in the brain.
And then the development of imaging like magnetic resonance imaging,
(01:58):
or MRI technology, has been really great because now we
can see these inflammatory lesions in the brain as they happen.
But that hasn't progressed us to a point where we
understand what is actually going on deep inside these lesions,
what's happening in terms of how the immune system is
being triggered and how the immune system is being activated
(02:19):
to start targeting and destroying parts of ourselves. And I
think the real advance has been, in the last couple
of decades, the understanding of the immune system and the
central role that it plays and the technologies that have
come along that have allowed us, even though we can't get
into these tissues, we can certainly now get to places
where we know immune activation occurs and start tracking these
(02:41):
cells at a single cell resolution that's going to allow
us to tell us what this cell is reacting to, and
why is it being triggered to react in that way?
Dr Viviane Richter (02:50):
What is the prognosis currently for patients?
Professor Tri Phan (02:52):
At the moment, one of the things that's really clear
is that MS has can run multiple different courses. And of course,
for a long time we've had clinical classifications based on
how it progresses. For some people, they have a relapse,
repeating course and other individuals, they may have a progressive course
where they have more and more attacks. And with each attack,
(03:14):
there's damage to the nervous system and they accrue more
and more disability. So what we're hoping moving forward is
develop an understanding that allows us to actually have a
better way to classify these individuals with MS, perhaps at a
molecular level. That might give us some insights into what
their future trajectory might hold, because that will really help
(03:35):
inform us in terms of what we can do in
the present to prevent that future.
Dr Viviane Richter (03:41):
Do we know why MS predominantly affects women and is
often diagnosed in young people?
Professor Tri Phan (03:47):
That is a really great question. And this sexual dimorphism
in terms of how men and women respond differently to
the environment, is something that's increasingly a source of great
interest because it goes to the core of how the
immune system works. That's a long way of saying we
don't know. And, in fact, that is one of the
(04:10):
big research questions that we want to address with the
OCCAMS research program.
Dr Viviane Richter (04:15):
Seyhan, can you paint us a bit of a picture of
where we're at with MS in terms of treatments and diagnostics?
Dr Seyhan Yazar (04:23):
So unfortunately there is no cure, I'll start by saying
that. But we have lots of therapies targeting and helping patients
to relieve them from their symptoms, and some of them
are actually helping to their immune system to fight and
the others like reducing some like inflammation in the body.
(04:45):
But MS itself is not a lethal disease, actually, but
the complications you get with MS can reduce an individual's
life expectancy 5 to 10 years compared to a normal person.
But the new treatments and the current therapies that we
have actually closing that gap greatly.
Dr Viviane Richter (05:05):
How is MS currently diagnosed?
Dr Seyhan Yazar (05:08):
So usually like patients visit their neurologist, and the neurologist does
like MRI scan, where they actually identify lesions. And if
those lesions are multiple and in certain regions of the
body of the brain, the patients are diagnosed with MS.
But that's the time that patients are actually have symptoms.
That's when the disease are already like made damage to
(05:31):
the brain. But prior to that time in the background,
there is some inflammation going on, and this is actually
a great opportunity for us to do some research to
identify individuals like early on rather than becoming symptomatic.
Professor Tri Phan (05:47):
Yeah, I think what Seyhan is describing here is a really
exciting opportunity. I think the goal for all of us
would be to actually to stop MS, and to do that,
we need to be diagnosing or predicting individuals who develop
MS before they've actually accrued any neurological damage. Because the
state of that right now is that we can't reverse
that damage. So our best bet is to stop it
(06:09):
from happening before it does.
Dr Viviane Richter (06:11):
So what does the virus have to do with all
of this?
Professor Tri Phan (06:14):
I think for a long time, because people really didn't
understand what the clues were that they were being told
from individuals with MS, we knew that there was a
strong genetic component. But the genetics doesn't explain all of it.
So that implies that there was a very strong environmental
driver of the development of MS. And, of course, one
(06:34):
of the most obvious things to propose then would be
maybe some sort of virus in the environment that we
didn't really know about. And, over the years, many viruses
have been proposed to be the culprit. The flavour of
the month, I guess, is this virus called the Epstein-Barr virus,
or EBV. This is a virus that many of your
(06:54):
listeners will be familiar with because it causes glandular fever,
or kissing disease, as it's also known as. This is
a virus that infects up to 95% of adults. And
so it becomes then really difficult, if so many people
get infected with it but so few people develop MS, what's
the connection? How do we tease apart the role of
(07:16):
the immune response to the virus and how that then
leads on to development of MS? And that's really the
sort of research that I think people like Seyhan are
really well placed to answer those questions.
Dr Viviane Richter (07:29):
What is the evidence to point to this virus?
Dr Seyhan Yazar (07:32):
Actually, there is a study that was done by the
US Defence Force. And that is the actual the most,
I think, clear evidence of showing that the Epstein-Barr virus is like
involved in MS. And so what they did in this
study is they have looked at their recruits since their start,
(07:54):
and they collected blood samples over years, many years. I
think the youngest like was like 15 years old at
the time of first study. And then, of course, they
came to an age of 45 when they were actually
diagnosed with with any kind of conditions, including MS. That
study gave us the actual causal relationship that we were
(08:18):
previously suspected. Like many, many years. We don't know like,
if it's actually causing the disease directly, or it's like involved,
like in a pathway that is causing another change, which
is like eventually resulting, like in MS. So that is
something that we are like trying to figure out in
the OCCAMS consortium by focusing on how especially the genes
(08:42):
within our body interact with the virus. And so what
is this changing in the body? What type of changes
it does so it can result in MS?
Dr Viviane Richter (08:52):
So how are you tackling this research question?
Dr Seyhan Yazar (08:55):
So, at the moment, we are recruiting MS patients. We
have already collected samples from healthy individuals. We designed a
study and we are waiting to complete our recruitment process.
Once we have all the samples that we have biobanked,
then we will look at different groups within our cohort.
(09:16):
And then we will compare these individuals and we will
do this at the single cell level. Look at the
individual immune cells within the body. We will look at
the gene expression. It involves a lot of like computational work,
which I am the expert, and that's how I'm like actually
involved in the OCCAMS study. What we will do is once
(09:36):
we have the data, we will use supercomputers to do
our analysis. What we are like hoping to achieve at
the end is to find some markers, some key signatures,
so we can then take these and look at how
they are involved by doing some laboratory experiments and validate
(09:57):
this in animal models, perhaps. And then that will allow
us to take this further for drug development or other,
like neurotherapies.
Dr Viviane Richter (10:08):
Tri, when did you first discover that working with Seyhan could
be beneficial for your research?
Professor Tri Phan (10:13):
So, I first heard Seyhan present her work at a
clinical translation school up in Brisbane a couple of years ago,
and she was talking about Onek1K. And I remember being
blown away by, not just what she'd done, but the
clarity with which she'd done it. To me, until then,
(10:34):
this whole thing about genetics and genomics and how DNA
influences RNA, it crystallised at that point, and she was
able to explain it in a way that a non-genetic
person like myself could actually understand then how your genetic
makeup can influence the expression of genes in an individual
(10:54):
cell that might play a key role in a disease process.
Dr Viviane Richter (10:59):
You established the OCCAMS consortium. Can you tell us what
it is and how that will tackle MS?
Professor Tri Phan (11:06):
I might start by saying I didn't really establish OCCAMS.
OCCAMS is one of those things where everyone put their
hand up. I just happened to be the conduit that
made it happen. The Open Coast-to-Coast Australian Multiple Sclerosis Consortium, or OCCAMS, really came
about from a conversation I had with Dr Jennifer Massey,
(11:29):
who is this incredible neurologist across the road from the
Garvan at St Vincent's Hospital. She is, in my mind, one
of the most knowledgeable person about multiple sclerosis, incredibly insightful,
and the conversation basically went along the lines of
all this amazing research going on at the Garvan, and we're
(11:50):
seeing all these people with MS in the clinic. Wouldn't
it be great if we could do something about learning
more about the disease and how we can help these
people and their families?" And so, out of that conversation,
we started thinking about what are the key assets, how
we can mobilise them, and how can we deploy them
in a way that would be really clinically meaningful in
(12:13):
terms of the questions that we tackle. And so, of course,
having recently heard Seyhan present, it was a no-brainer to
think that, actually, a central part of our research program
would then revolve around how we can use the sort
of tools that Seyhan developed in her research with Joseph
Powell to then help us answer the questions that we
(12:36):
wanted to ask about MS. And I think OCCAMS is
really exciting because we were able to mobilise experts in neurology, immunology, genetics,
expert clinicians who are expert in looking after people with MS,
and scientists who have been studying autoimmune diseases across the
(12:58):
country and actually across the world, because we have in
our consortium experts in the UK, in Germany and in
the United States. So I think, really, when you have
a difficult problem like MS, it's gonna take a lot
of different ways of thinking. And I think one of
the great joys that I have in research is being
(13:21):
able to sit in a room with incredibly bright people
who know so many things that I haven't even dreamt of,
and just sitting back and watching them brainstorm and work
out ways. They may not come up with a solution,
but you sit there and you realise if a solution
is going to come, it's going to come from the
people in this room.
Dr Viviane Richter (13:40):
How close are we to eradicating this disease?
Professor Tri Phan (13:43):
My hope is, potentially for some people far fetched, but
I really do think we are now at a crossroads
where all the ingredients are there for us to potentially
maybe stop MS before it happens. So the dream I
think that we all share is the idea that maybe
(14:04):
one day we'll be able to eradicate MS, in the
same way we've been able to eradicate smallpox, by mobilising
the power of the immune system.
Dr Viviane Richter (14:13):
And Seyhan, how hopeful are you that your research will
have a lasting impact for MS patients?
Dr Seyhan Yazar (14:19):
Of course, we cannot change our genetics. That's what we
are born with. But we are aware of what environmental like
factors that we can be exposed to, and our hope
is to be able to diagnose individuals who are likely
to become MS patients before their actual diagnosis. There is
(14:39):
actually a very great interest in this type of research
at the moment. There is a period called MS prodrome,
where someone has some symptoms. But these symptoms are very common,
like fatigue, headache or some urinary tract infections, which is
(15:00):
very common for people normally healthy to have. But those
symptoms are also occurring in MS patients. So, at the moment,
we are trying to identify these key events in someone's
life by monitoring them way before actually they become MS patients.
(15:21):
So one approach that we are doing is we are
collaborating with Liverpool Hospital researchers, where we are looking at
their medical health records and seeing what type of problems
and presentations patient had prior to their diagnosis of MS.
Our hope is to identify key symptoms that could lead
(15:47):
us to understand when MS diagnosis like is happening. What
we'd also like to do is, not only use this
like the information that we get from the electronical medical records,
but also from their blood samples to see if we
can see these early signatures within the blood. But this
(16:09):
is one of the long term goal of OCCAMS consortium
because doing a research and doing it on a disease
like MS will take lots of years. So for a
medical research to actually come with a conclusion, come with
like some treatments, actually takes almost like 20 years. But
(16:29):
we are very hopeful, and we are very excited that
we are at the beginning of this work. And we
have a great team, older like researchers, as Tri has like mentioned,
that are capable with lots of different skills and expertise.
By bringing everyone together, applying these new technologies and approaches,
including artificial intelligence, we are hoping to like come up
(16:53):
with some model or like some prediction of who's going
to become more likely to become or have MS in
the future. And once we do that, then it will
be very easy for us to actually stop and eradicate MS.
Dr Viviane Richter (17:09):
Why is Garvan the place for you to be doing
this research?
Professor Tri Phan (17:12):
I would say Garvan is a really exciting place to
work at, especially now, because we have this seamless integration
between the institute and St Vincent's Hospital next door. So
that dialogue between clinicians and scientists is really, really important
because it really grounds the research and makes sure that
(17:33):
we're asking really important, clinically meaningful questions. But beyond that,
within the Garvan itself, we have some really brilliant minds,
really creative people who are thinking differently. And along with
that comes some really amazing cutting edge technologies that really
(17:53):
allow us, as Seyhan has described, to be able to tease apart,
at the single cell level, the molecular footprints that might
tell us how a cell has been exposed to environment.
And then how it's changed itself in such a way
that now it's become a cell that actually is attacking
the central nervous system. And I don't think there are
(18:15):
many other places in the world that would have all
those things in one place.
Dr Viviane Richter (18:22):
Seyhan, we can hear the enthusiasm in your voice for
this research. What motivates you day to day?
Dr Seyhan Yazar (18:29):
Well, I guess my love of science. I have to
mention that first. But I think being in the clinic,
seeing patients, seeing patients with genetic disorders that sometimes that
you cannot change is really affected me. I think I
am feeling grateful. The work that I will do will
(18:50):
contribute a little bit to the potential treatments and maybe
featuring some cure that might be possible that can actually
change their life.
Dr Viviane Richter (19:04):
We look forward to hearing the outcomes of this incredibly
promising research. Now, before you go, we'd like to get
to know you a little bit better. This section is
called the Fast Five. What was your first job?
Dr Seyhan Yazar (19:18):
I was a tutor and I was teaching year five
and six students. It was fun. They really didn't want
to do a lot of maths. So it was a
bit challenging, but at the end, I think they were grateful.
Professor Tri Phan (19:32):
My first job. OK, so that would have been after school.
I was a kitchen hand in the Queen Victoria building,
making deep pan pizzas and washing dishes.
Dr Viviane Richter (19:43):
Look how far you've come.
Professor Tri Phan (19:44):
I'm still washing dishes.
Dr Viviane Richter (19:47):
Do you have a favourite movie?
Dr Seyhan Yazar (19:49):
I think A Beautiful Mind was my favourite movie. It came out,
I think, it was at high school. And when I
learned the story of the Professor, I was like, really intrigued.
So it really touched me. It's still, I think, remains
as my favourite movie.
Dr Viviane Richter (20:10):
Do you have any secret skills?
Dr Seyhan Yazar (20:12):
No secret, but I love cooking and my family and
friends really enjoy when I cook. I do too, so
they really enjoy when I make lots of Turkish dishes.
Their favourite being this dish called, very traditional, called beans
with rice, which is very traditional, very simple dish. But
(20:32):
it's really warming, especially during winter days.
Dr Viviane Richter (20:36):
Something that's on your bucket list?
Professor Tri Phan (20:38):
A long time ago, I had this idea that I
wanted to climb the north face of El Capitan. I'm
in no condition to climb it now, so definitely that
would now qualify as a impossible bucket list thing to do.
Dr Viviane Richter (20:51):
Do you have a favourite quote or life motto that
resonates with you most?
Professor Tri Phan (20:56):
"Everything's connected" from Dirk Gently's Holistic Detective Agency. Because I think,
at the end of the day, a lot of what
we do in science is trying to draw connections together.
The challenge, though, is and one of the great pitfalls
is that the human mind is very capable of seeing
connections where they don't exist, and that is where we
can fall.
Dr Viviane Richter (21:17):
Seyhan, how about you?
Dr Seyhan Yazar (21:18):
"When one door closes, another will open". It's really easy
to be trapped with pessimism. When you're a scientist, when
you're what do you want to achieve? You are not
there to achieve it yet, or you don't have what
you need to have to achieve it. And so you have
to remain optimistic. And that's the optimism that we need
(21:41):
to pass to our patients as well, that there will
be a hope for them in the future.
Dr Viviane Richter (21:47):
Professor Tri Phan, Dr Seyhan Yazar, thank you so much for
joining us on Medical Minds.
Dr Seyhan Yazar (21:53):
Thanks for having us, Viv.
Professor Tri Phan (21:55):
Thank you, Viv. It's always a pleasure.
Dr Viviane Richter (21:57):
If you'd like to know more about this research or
donate to the work we do at Garvan, head to garvan.org.au.
And if you've enjoyed this podcast, please leave a review
and share with other podcast lovers. I'm Dr Viviane Richter.
Thanks for listening. This podcast was recorded on the traditional
(22:18):
Country of the Gadigal people of the Eora Nation. We
recognise their continuing connection to land, waters and community. We
pay our respects to Aboriginal and Torres Strait Islander cultures
and Elders past, present and emerging.
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