Yesterday, Dr. Mark Scott, researcher at the Cochin Institute in Paris, was awarded the Elsevier-Cochin Innovation Award by the Paris Descartes Foundation together with Elsevier. During the award ceremony at the Université Paris Descartes, the president of the university, Dr. Frédéric Dardel, recognized Dr. Scott’s research project and presented the award.
Afterwards, Elsevier’s Petra Ullrich interviewed Dr. Scott about his career and research project. Here is an edited version of their interview.
Congratulations for receiving the Cochin Institute-Elsevier Innovation Prize. Could you please tell us a little bit about you and your research?
Thank you – we appreciate the support attributed by the Elsevier Innovation Prize for our research. I have been working at the Cochin Institute here in Paris for over 10 years now as a CNRS (French National Centre for Scientific Research) scientist. I'm originally from Scotland and carried out my undergraduate and PhD studies in the UK. Next, I was fortunate enough to obtain a Wellcome Trust International Prize Travelling Fellowship, which allowed me to train as a postdoc both at the Cochin Institute and the MRC Lab for Molecular Cell Biology in London before moving to France permanently.
About my research: The PI3K/AKT signal transduction pathway is a key regulator of cell proliferation, survival, migration and invasion. Loss of proper control of this pathway is a recurrent theme in most types of cancer. The tumor suppressor protein PTEN acts as a brake on the PI3K/AKT pathway. My group investigates how the regulation of PTEN controls this pathway and how PTEN function may go awry in different cancer contexts.
What were the main steps you went through during your research process that led you to create this innovative project?
In the lab, we have a longstanding interest in harnessing new technology to probe protein function. A few years ago, we developed a biosensor for PTEN, based on a technique called Bioluminescence Resonance Energy Transfer (BRET) that occurs naturally in some marine species. The biosensor enables us to follow changes in PTEN conformation or "protein shape" in living cells. Using the biosensor we have been able to detect changes in PTEN conformation that are associated with enhanced PTEN function.
As PTEN function is often decreased in human cancers, restoring or enhancing its activity could present an effective therapeutic strategy to combat cancer. Last year, in collaboration with researchers at the Institute for Research In Immunology and Cancer in Montreal, which has an ultra-modern screening facility, we used the biosensor to start to screen large collections of chemicals in an attempt to identify tool compounds that impact PTEN function. We have now completed the screen and identified a series of "chemical hits." The Elsevier Innovation Prize will help us in our goal to characterize how these molecules influence PTEN function.
How would you describe the societal value and utility of your research? How would you present your research to the public?
The Cochin Institute is situated on a large hospital site in the center of Paris. There are three different types of ongoing research: basic or fundamental research to increase our understanding of how things work in biological systems; clinical research; and translational research where, for example, new ideas can unveil potential therapeutic avenues to explore or lead to the development of new technologies.
The first basic research goal of our group is to try and understand how PTEN is regulated normally and how it may become deregulated in cancer settings. The second more applied goal is to determine if decreased PTEN function can be restored or enhanced in some way, which is what we are currently aiming to do with the screening project. Therefore, I consider the societal value and utility of our research two-fold: the first is to increase our basic knowledge around how PTEN is regulated/deregulated and the second is more translational with the goal of enhancing PTEN function using a chemical biology approach, which may provide therapeutic avenues to explore. It's also important to highlight here that the translational component of our work stemmed from our fundamental research into PTEN.
I would summarize our research to the public as follows:
A cellular communication pathway driven by two oncogenic proteins called PI3K/AKT is often overactivated in cancer. The design of small molecules to inhibit these oncogenic proteins has provided the main approach for the development of anti-cancer therapeutics targeting this pathway. Indeed, over 50 drugs inhibiting this pathway are in development, and many clinical trials are ongoing, with several drugs now approved for clinical use. The tumor suppressor PTEN acts as a "natural" brake on the PI3K/AKT pathway. However, using small molecules to re-activate tumor suppressors, has been much less explored as a potential anti-cancer approach. Our project is therefore aimed at investigating this possibility, which may in the longer term offer future therapeutic opportunities.
Today, researchers not only need to achieve results, they need to be able to communicate and make them understandable to a broader public. How important do you think this skill will be in the future, and how did you learn to communicate about your research in the most effective way?
Researchers are continually asked to present their research in different formats to other scientists that are non-specialists in their research field and of course the general public. This skill is already key in our profession and will continue to be important into the future. The different number of communication tools has also increased tremendously over the past few years with an emphasis being put on getting your message across succinctly in an "elevator pitch" manner.
In the context of developing these skills, I've been involved with teaching English Scientific Writing to PhD students at the University of Paris. As part of a teaching team, I helped train them to write short and attractive abstracts on their own work. Of course, this sort of exercise also makes you reflect and helps analyze how to present your own work in an effective manner.
What other advice would you give to a young researcher starting his/her research career?
Choose a subject area that you are interested and passionate about and keep a positive mind-set about your research. People will always be around to tell you something isn't good enough or not to waste too much time on a certain experiment, but if you're convinced about something, go ahead, stick with it and see it through. In line with this, I like to quote the (Persian) poet Saadi for my trainees: “Have patience. All things are difficult before they become easy.”
If the opportunity presents itself, international mobility at some point during the career is also definitely worth pursuing. In addition to the life experience, learning how research is done in different environments and with differing approaches is a very enriching process.
What would be the next great question you would like to answer in your research?
I'm eager to advance on the projects we currently have and to move forward with the characterization of how the molecules we have identified influence PTEN function.