Dr Tamara Chessa, a postdoctoral research scientist in the Signalling research programme, is the Institute’s 2023 Sir Michael Berridge Prize winner. The award was endowed by Sir Michael who was a group leader at the Institute from 1990 until 2004, after which he was appointed the Institute’s first Emeritus Babraham Fellow, a position he held until his death in February 2020. The award recognises the contribution of a PhD student or postdoctoral researcher to an outstanding piece of published science, in this case Tamara’s paper ‘PLEKHS1 drives PI3Ks and remodels pathway homeostasis in PTEN-null prostate’. In this profile Tamara talks about receiving the prize, her research, and her family.
Could you tell me a bit about your background and your career so far? How long have you been working at the Institute?
I grew up in Delft, The Netherlands, and studied Biomedical Sciences at the University of Amsterdam. While studying there, I developed a keen interest in signal transduction. I was fascinated by how molecules signal to each other as part of a complex network of communication and how this is tightly orchestrated, so that our cells can function properly. In parallel, I had a long-standing interest in cancer research.
I went on to do research placements at the Erasmus MC in Rotterdam and the Netherlands Cancer Institute (NKI) in Amsterdam. After a great experience studying phosphoinositide biology in C. elegans in the lab of Dr Nullin (Nal) Divecha at the NKI, I was looking for an experience abroad and Nal said that he knew the perfect lab!
I loved being in Len and Phill’s lab so much that, after finishing my degree, I came back to the Babraham Institute for a PhD and never left! Dr Teun Munnik, my supervisor at the University of Amsterdam, called it ‘the magic of Len and Phill’s lab’ – a special place to be - and he was right!
Did you always want to be a scientist?
Since being a teenager – yes, I did. My father died of cancer when I was in my teens and I wanted to learn about the biology of cancer, with the ultimate hope and wish that I could contribute my own research and expand the knowledge and understanding of this important subject. During my time at secondary school, and thanks to a fantastic biology teacher, Mr Kroese, I recognised that basic research forms the foundation for improvement of current therapeutics.
Talking about inspirational people, I’d also like to mention Prof Jannie Borst. She was the head of the Immunology department at the NKI while I was there for my research placement during my Masters degree and was extremely passionate about her research.
I also have a great interest in the arts and considered applying to academy of visual arts in The Hague. Inspired by many of my family members, who are artists, I have enjoyed drawing with pastels as well as painting with oils and acrylics.
How did it feel when you heard you had won this year’s Sir Michael Berridge prize?
I was very emotional and felt extremely grateful for the recognition of this work. I’d like to acknowledge the huge team effort that was required to achieve this publication. In particular, Arqum Anwar, Sabine Suire and Piotr Jung, who have made great contributions to this work. I am tremendously grateful to Len and Phill, for their advice and their support, on both a professional and a personal level.
I’d like to dedicate this prize to my father, Giovanni Chessa, and to my mother, Elena Chessa. My parents grew up in poverty during and after the Second World War in rural Sardinia and did not have the opportunity of education beyond primary school. My father emigrated to The Netherlands in the 1960s and worked in the coal mines in order to support his family. He went on to work at the Dutch Cable Factory (NKF), went to secondary school at the same time and worked his way up to head of department over the years. My parents’ strong work ethic and optimism has always been a source of inspiration to me. I’d also like to mention my brother, Tony, and my sister, Tiziana, with thanks for their unwavering encouragement and support. And very special thanks to my husband, Erez, and son, Isaac, for all the love, fun and joy, every day.
What was the goal of this research?
Phosphoinositide 3-kinases (PI3K) are enzymes that orchestrate a variety of essential cellular functions such as cell proliferation and survival. The PI3K signalling network has been studied for many years at the Babraham Institute, but because it is so complex, we still don’t have a full picture of all the interactions between signalling proteins. This research was part of a large-scale project aiming to identify the regulators of PI3K signalling in our healthy cells and tissues, and in disease.
Our approach was tagging the PI3K subunits, as they occur naturally in our cells and tissues. We achieved this by introducing small genetic modifications (tags) in the genes encoding PI3K subunits in mice. The genetic tags allow us to rapidly ‘fish out’ the PI3K subunits from tissues and subsequently identify their interacting proteins.
In prostate cancer, mutations and deletions of a tumour suppressor called PTEN are very frequent, especially in advanced cancers. PTEN acts like a brake in the signalling network that PI3K drives. So this left us with the question of what regulates PI3K signalling in prostate cancer when PTEN is inactivated.
We set out to investigate what the regulators of PI3K signalling were in healthy mouse prostate vs a mouse model for prostate cancer. We were able to show that the network is remodelled in cancer cells to the extent that the activators of the pathway change. Discussions with Prof Julian Downward helped shape this project.
Was there a moment of discovery during this research?
Without a doubt, the discovery of the protein PLEKHS1 in our search for regulators of PI3K signalling was unexpected! We had never heard of PLEKHS1 before, and indeed, it was poorly studied. We are still amazed that PLEKHS1 turned out to be a key activator of PI3K signalling, as well as a key driver of cancer growth in the PTEN-null mouse model for prostate cancer. Intriguingly, PLEKHS1 appears dispensable for healthy prostate function.
In addition, we discovered that loss of tumour suppressor PTEN leads to a dramatic remodelling of the PI3K signalling network. This challenges the current dogma that genetic mutations in PI3K pathway components in cancer simply lead to over-activation of the PI3K signalling pathway.
What are the next steps for this research?
We aim to explore the diagnostic and therapeutic implications of our findings and are currently in discussion with commercial partners. Highly relevant to this is finding out what’s upstream of PLEKHS1 activation. We are currently exploring the potential role of inflammatory mediators that are prevalent in the PTEN-null prostate. As part of this project we have recently started a collaboration with the Samant group at the Institute. Our findings could have implications for healthy ageing research.
What’s your favourite part of being a researcher and working at the Institute?
The best part of being a scientist is, in my opinion, discovering how things work in a cell and finding out something that was not known before. However, hypotheses can often turn out to be wrong, experiments may not work, or might not lead to positive data. This is a key part of being a scientist: it is important to persevere, and you will ultimately find a research question that will yield results. When this happens, and you make a new discovery, it is an amazing feeling and a unique experience for a scientist compared to other careers. I like to talk about this to students that have come to our lab for research placements over the years. I really enjoy supervising students and generally I think I have learned as much from them as they have from me. Working as part of a team and interacting with other scientists is always a great pleasure, and our research has greatly benefited from collaborations, both within and outside the Institute. I highly value being part of a research institute where world class research is being undertaken. This is in large part thanks to the state-of-the-art facilities and support services that make our research possible. I have met many lovely people at Babraham, some of whom have become friends for life.
04 December 2023