Summary:
As you watch the video, listen to what Nikki has to say about:
Captions:
So a particular gene that I have been working on for a number of years is PP2A,
and you’ll notice scientists always use abbreviations
and a lot of this has got to do with the fact that we write on tiny little tubes like this
and if I was to tell you the whole name: protein phosphatase 2A
trying to write that on a tiny little tube about a thousand times over gets a little laborious.
So, we tend to abbreviate pretty much everything but all you need to know is that this particular gene called PP2A
had been found to be mutated in some types of cancers.
So, it’s a gene that encodes for a protein, so the worker in the cell that’s involved in lots of different things
within the cells but importantly it’s involved in normal cellular growth. So it has to be there for cells to grow normally.
But it’s also what we refer to as a tumour suppressor.
So under the normal situation one of the roles of this particular gene is to protect cells from uncontrolled growth.
So when it’s there the cell knows when it gets to that limited life span:
that the red light comes on it’s time for you to stop growing.
The problem occurs when we get a genetic mutation in the gene
or when we completely turn off this gene within the cells,
the cells suddenly have no protection against that and the green light basically comes on.
So mutations in this particular gene have been identified in some types of cancers including breast cancer
and leukaemia and these are two of the cancers that I work on.
Summary:
As you watch the video, consider the following questions:
Captions:
So really, the first research question that my group asked was, does this mutant PP2A actually cause cancer?
And so to do that, obviously we can’t take people and come along and give you a mutant PP2A
and say lets’ see what happens?
There’s a few ethical issues involved there.
So what we use in the laboratory is basically a laboratory model of cancer.
And for this particular work in the breast cancer we’re using cells that are derived from normal breast tissue.
So if we just have look at the architecture within the breast you can see we’ve got lots of these mammary glands
they’re the functional components obviously of the breast.
And if we actually have a look at the microscopic level within these mammary glands we’ve got these individual cells
making up this sort of rounded structure here and we’ve got a hollow lumen inside.
So this is what each of these mammary glands look like if we were to cut a cross section through them.
What happens in breast cancer we lose this really structured architecture,
instead of having this nice what we call polarised cells around here they’re all lined up perfectly.
In breast cancer the cells obviously undergo uncontrolled cell growth we’re getting too much cell division in these,
these breast cells, so that we start getting a tumour formation.
We lose this nice ordered structure and this is really where we start getting a lump.
So, we can actually mimic this in the laboratory.
So what we do is we take normal cells from a patient, so this would be a woman without breast cancer,
normally who’s under going a breast reduction surgery or something like that,
and we can take those normal breast cells
and we can grow them in specific conditions within the laboratory
so that they form these highly ordered mammary gland structures.
And what we are actually looking at here this is a cartoon
So it’s a three dimensional structure of one of these glands
and we can use florescent microscopy so we can stain each of these individual cells with particular dyes
that will come out different colours.
When we then use a high powered microscope to look at the individual cells.
And this is what a normal breast cell grown under these conditions in the laboratory looks like.
When we then take cells from a cancer patient from a tumour,
from a breast; you can see we have this uncontrolled growth.
So we have multiple forms of these glandular type structures
all growing on top of each other and we don’t have this hollow inside any more.
The cells continue to grow and so we get this, basically mass of cells.
So we can use these types of models in the laboratory to try
and work out what’s the difference between this cell and this cell.
Summary:
Listen to Nikki’s talk about cancer mutations and think about:
Captions:
What we do for this particular question we are interested in, our going back to our PP2A,
our gene that’s mutated in different types of cancers and we take that gene,
that mutant PP2A gene and we insert it into a normal cell.
So we take our normal cells from our healthy patient
and we take our PP2A gene and we insert that gene into the cell.
Sounds really easy-takes about six months to do unfortunately.
But when it works it's great.
So we’ve now got cells growing in a culture dish in the laboratory that have our mutant PP2A gene
and we can compare them to the original ones
that don’t have the mutant gene and we can ask the question: well have they become cancerous?
And this just gives you an example of some of the types of results we get when you do this.
So here we just looking at our normal cell,
if we look under a standard light microscope you’ll actually see all of these individual cells around here.
When we then look at a cross section through that with fluorescent dyes,
so the green we’re looking at the individual cells around the outside of this glandular structure
and red we’re just marking the very outside edge and this is what we see in a normal cell.
It looks similar to that cartoon I showed you before.
When we insert our mutant PP2A you can see we get this really bizarre growth going on.
There’s lots of fluorescent green cells all throughout the middle of these structures,
they’ve lost their nice round formation and we’re getting over growth.
So the answer is ‘yes’ these mutant PP2As do actually cause cancer in these particular breast cells.
So we’ve answered our first question. Obviously, then what we want to know is well o.k.
if we know that these particular mutations in this gene cause cancer can we use them
to come up with a new therapy against these cancers?
Summary:
As you watch the video, consider the following questions:
Captions:
We are continuing to do the work with breast cancer but we are a little bit further ahead in our leukaemia work,
which also has mutations in PP2A and it looks like ‘yes’ we may be able to use this to our advantage.
So this particular drug is called FTY720 – it doesn’t matter what it’s called.
Basically, it is a drug that we’ve shown reactivates normal PP2A.
So we can throw this into our cancer cells and we can reactivate our PP2A. We look at nature and we try
and emulate that and virtually every drug that’s on the market
or and a lot of them that we’re investigating further have come from nature,
they’ve come from marine organisms, from bacteria, from plants
and then we get the chemists to figure out exactly which part of those materials
that we’re interested in and to develop purified formulations of those particular drug
and FTY720 is exactly the same.
But anyway we’ve shown that this drug can reactive our PP2A
and when we throw this into cells our leukaemia cells
so leukaemia cells that have the mutant PP2A compared to normal cells that don’t
when we treat with this particular drug
we inhibit the survival of these cells, so we kill these cells off.
So, at least in our model systems within the laboratory
this drug is looking really successful in terms of killing off the cancer cells and not affecting normal cells.
And we’re following this up with some further studies now.
Summary:
As you watch the video, consider the following issues:
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So I guess what I just want to leave you with is now a bit of an idea
why it seems to take so long for research findings
like this, which is a really exciting research finding.
Well that’s great lets just throw FTY720 into patients and see what happens.
Unfortunately, it takes a lot longer than that and you hear all these new stories:
oh there’s been a research breakthrough but it’ll be five to ten years before, you know,
it’s going to get to any patients and really that’s because we’ve got this long research timeline.
So the type of work that I’ve been speaking about is really at this pre clinical stage using our basic biology,
our basic bio-chemistry to understand a disease: to identify what’s different between normal and cancer
and to come up with, potential new therapies. This then has to then undergo a number of phases.
and actually getting this compound ready for use in humans.
We go through a phase zero where we do some more animal studies
The compound then has to undergo phase one studies to see that it’s safe in humans;
obviously we can’t just give it to every patient who has a particular disease and hope it’s going to be safe.
Once it’s been shown to be safe it then goes through a clinical trial
so that we can really look into exactly how effective
this particular drug is - is it any better than what we’ve got?
Because if it’s not there’s no point in going further ahead and this will then develop,
if it gets through this first phase, into a phase three clinical trial
where we’re now looking at a much larger body of
larger number of patients. We’re really looking to see how effective this particular drug is.
And if it gets through all of this it will eventually be approved by the relevant authorities
in which ever country you’re working in. And you can see that as we’ve gone along the amount of time
and the amount of money that’s invested in this significantly increases
and unfortunately the number of successes decreases.
So we hear a lot of information about these wonderful breakthroughs up here,
unfortunately they don’t all end up being therapeutics. But a small proportion do
and as I mentioned we’ve seen this decrease in the number of patients dying from cancer, so it’s those successes
and those success stories that really keep people like me going
and that keep all investment in cancer research going.
Summary:
Listen to Nikki’s talk about the nature of research:
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I am just going to finish off and give you a bit of an idea of what I think medical research
and in particular cancer research is like as a career.
And I think the most important thing is that it’s extremely challenging
you very rarely get bored in this industry
you’re doing lots of different things: you’re working in a laboratory,
you’re asking questions all the time and trying,
figuring out ways of answering those questions so you’re constantly challenging yourself
and you’re not doing the same thing.
You’re not stuck in front of a computer all day, you know, you’re in and out of the lab.
You get to travel the world which is really important, I think.
Each year we’ll go on at least one overseas conference.
Most people once they’ve finished their studies will go overseas to do a post doc,
so postdoctoral studies so you pretty much pick where you want to go
and find a lab that looks good there to go to.
So – and its fun.
If you’ve got to do something every day for the rest of your life you want to enjoy it
so you want to find something that you’re passionate about
and that you enjoy. And of course it’s rewarding
if you understand more about the human body then we can actually lead to better health outcomes
and that‘s got to be rewarding for anyone.
I guess not necessarily a negative side, but it’s a lot of hard work like any type of job.
If you want to excel at it you’ve got to put the effort in but if you enjoy what you’re doing it doesn’t feel like an effort
and it can take a little bit of time before you start getting any type of real money
because it does take a fair amount of time to do your study but you’re going to find that with most things.
Summary:
As you watch the video, listen to how Nikki describes her study and research career:
Captions:
So really what you need to get there, is I think, a passion.
You need a passion for whatever it is you’re doing whether it’s biology, chemistry whether it’s not science.
There’s no point doing something unless you’re passionate about it so you need that ambition and that drive
and I think in any type of science career you need to have an inquisitive nature.
Really we’re all really interested in science because it can give us the answers to why things work,
why things don’t work so that inquisitive nature I think is really important.
And I guess in terms of bio-medical research, obviously an interest in biology and chemistry is important.
Trying to understand how the human body works has always interested me,
so any type of career in that area was what I was going to be following up.
Things like why - what goes wrong in disease situation and how we can use our knowledge to treat that disease,
as I said, can also be really rewarding.
So in terms of actually getting there for myself it started off with a Bachelor of Science
so this was three years at university and then an extra year of just research.
So not going to lectures anymore and not doing exams
but actually getting in the lab and getting you’re hands dirty
and asking questions and doing experiments which is where the real fun begins.
At that stage there was really only science that you could do or medicine,
there’s lots of other new degrees out there now.
Things like biomedical sciences, biotechnology that are available if you’re interested in this particular area
and there’s a lot of great new courses available at all the universities around New South Wales and nationwide.
Like all of us, we then went on to do a Doctor of Philosophy,
or a PhD which sounds like a long time it’s another three to four years full time,
but again this is all in the research laboratory so it’s not like going to classes it’s actually doing a research project
and it’s at about this stage you start to get a little bit of money.
The government will give you a scholarship to do this for three to four years
and obviously after that you’ll go on and work.
So the types of fields it can open up, any of these types of degrees obviously are huge.
Medical research, which is my particular interest, you can go into things like drug development
and forensic science which is a really hot topic at the moment.
Veterinary sciences, health care delivery so you might actually want to down more of a career
or becoming a doctor
actually treating patients as opposed to being behind the scenes or developing healthcare policy.
And ,I guess what I really want to leave you with is,
if you don’t get into your first choice,
if you’ve all got an idea now right, this is what I really want to do,
I want to become a doctor or I want to do this.
Well you’re lucky to start with if you do know what you want to do because I certainly didn’t.
But there are plenty of ways of getting there
if you don’t get directly into what it is that you want to do straight from school.
Don’t panic. There are lots of ways of getting there.
I initially thought I wanted to become a doctor and so I thought right I’ve got to do medicine
didn’t get in straight from school.
What do I do? So I did science and I could have got there from science but I decided
nah I think I’ll stick to this research side and I wouldn’t go back.
So you might find something better along the way as well. Keep the passion and the drive
and you’ll do well at what ever you choose to do and try and remember to have fun,
it’s really important to have a life as well.
And if it’s not satisfying you, what you’re doing, find something else to do.
Thanks very much.
Students: Applause
Music: Music