Knowledge impact case study: The enzymes protecting our cells

Professor Christina Mitchell, Head of the Mitchell Laboratory at Monash University is investigating the enzymes that regulate cell proliferation and the critical role they play in suppressing tumour growth.

Through her pioneering research into cancer biology, Professor Mitchell is helping uncover new insights into how cancers develop and identifying potential pathways for future treatments.

Meet the mind behind the research in our latest knowledge impact case study – part of NHMRC's 90th anniversary celebrations. 

Video transcript

0:06 Professor Christina Mitchell
Well, I've been working in this area for several decades, and I was inspired to do it because I started working my postdoc on the first member of what turned out to be a large enzyme family that regulated membrane lipids. And I purified the first enzyme in my postdoc and then came back funded by the NHMRC when I came back as a senior lecturer. And I cloned the enzyme and then discovered that there were actually 10 other family members. And so these enzymes regulate membrane signalling and change the way the membrane responds.

0:45 Professor Christina Mitchell
And at the time, because I was a haematologist, I was very interested in cancer and the field was expanding. PI3-kinase had been discovered. My enzymes regulated PI3-kinase signalling, which is a major oncogenic cancer.

So, then we systematically started to knockout these genes and we got very surprised because they didn't cause cancer, they caused muscle disease and muscular dystrophies, or they caused changes in embryonic development. And more recently they seem to be associated with rare human developmental syndromes called ciliopathy. And when these genes are mutated, there are developmental defects that lead to quite serious developmental problems in children.

1:25 Professor Christina Mitchell
And so, from the expectation that I had these biochemically characterised enzymes that regulated membrane signals, when you actually do the functional studies and look at knockout mouse models, and then subsequently on the basis of those human disease mutations, we were very surprised. It led to many different areas of research and how important these particular enzymes are in terms of human development.

I'm intensely curious about why things work the way they do and follow that train in terms of discovery research, which has had a big impact in terms of actually leading to diseases that we didn't know existed due to mutations in these genes.

It's been a voyage of discovery. So, I'm in a way driven by the curiosity of science and how basic science can actually lead to enormous discoveries in terms of clinical disease. And by understanding the fundamentals of cell biology, it can really help you understand disease processes.

2:27 Randini Nanayakkara
So, I work on muscular dystrophies and myopathies, and these are very rare, rare but very severe muscle disorders.

And currently there are no treatments available and one of the disorders I'm working on, it's a very severe paediatric disorder and I have a very young son. So, this project is very close to my heart and whatever little contribution I can make towards a future potential therapy would make me really happy.

2:54 Emily Jones
I work on understanding disease mechanisms in breast cancer.

I've always been really fascinated about the complexities of cancer and cell signalling, so this research in Chris's lab was really fascinating to me.

3:06 Professor Christina Mitchell
When I started, they said we think there's this enzyme, go find out and purify it, and then we cloned it and then we characterised it. I think the advantage of understanding the molecular basis of disease, it can help you develop treatments for that disease.

3:23 Emily Jones
So I'm looking at the role of phosphoinositides and phosphatases in breast cancer. And this is really working on building on the work that Professor Mitchell has been doing over the years as her lab has been a really pioneering research lab in the phosphoinositides and phosphatases signalling space in all wealth of diseases.

3:44 Professor Christina Mitchell
It turns out that my research really impacts on a suite of rare diseases, and it's rare diseases in muscle and rare diseases, developmental diseases and a small subset are probably associated with cancer.

I think it's a discovery that these diseases are caused by mutations in these genes.

I get letters from people who have these rare muscle diseases saying we're holding out hope that your research can find a cure. That's very confronting, but also very incentivising to say, we have discovered they're mutated, we're working out how it works and what happens when they're mutated in a hope that we can find a treatment.

We're optimistic, but there is still a way to go.

4:29 Randini Nanayakkara
Currently, there are no therapies for these disorders. You can't really develop a cure either. So, if we can develop a therapy that could manage these disorders, that's the goal and we are working towards that, to give these patients a better quality of life.

4:46 Professor Christina Mitchell
Well, I'm an enormous admirer of NHMRC. I've been the beneficiary of grants from the NHMRC my entire career. And also, I've worked with the NHMRC in reviewing grants and being on various committees.

I think it's a wonderful organisation. I think peer review is essential.

I've trained 35 PhD students on the basis of NHMRC grants.

The effect of the NHMRC grant is not just on the individual researcher who's awarded the grant, which has been me over, you know, a 25-year period. But also, that PhD students I've trained, have been trained basically on the basis of the NHMRC grants I've received.

They've gone out into the world. Some of them are schoolteachers, heads of science departments. Some of them are running their own labs. Some of them have gone into commercialisation.

So, it's inspired that, you know, NHMRC grants actually trained a whole legion of people into the future as well.

And that's one of the great things I like about doing science, mentoring young people, young PhD students, early career researchers, to the excitement of the science.

And they take that knowledge and then use it in many different ways.

5:50 Emily Jones
We wouldn't be able to continue on with our research if it wasn't for the ongoing support of the NHMRC.

End of transcript.