EACR Travel Fellowships are sponsored by Worldwide Cancer Research and provide funds up to €3,000 to early-career cancer researchers. For more information on how to apply for Travel Fellowships, you can visit the EACR website.
Home institute and country: Trinity College Dublin, Ireland
Host institute and country: Cold Spring Harbor laboratory, NY 11724, USA
Dates of visit: 11 July – 17 August 2018
Obesity is the leading preventable cause of cancer worldwide. We believe this is due to the body’s anti-cancer immune cells not working properly in obese people. Indeed, our lab recently discovered that crucial anti-cancer immune cells called ‘Natural killer (NK) cells’ are dysfunctional in obese people. In addition, we found that fat signals are strongly ‘turned on’ in obese NK cells. My research placement aims to understand whether the ‘turning on’ of these fat signals is causing the dysfunctionality of NK cells in obese people. This research helps us understand why obese people get cancer for future therapeutic interventions.
I was eager to learn a new scientific technique in a world-renowned research institute of excellence, while benefiting from the cultural experience of working and living in America.
How did you hear about EACR Travel Fellowships?
I heard about the EACR travel fellowship from my lab colleague Dr Lydia Dyck, who is an ambassador for the EACR. I decided to apply with the EACR because of the scientific and personal value of such a prestigious award. I was eager to learn a new scientific technique in a world-renowned research institute of excellence, while benefiting from the cultural experience of working and living in America. I am now excited to bring the knowledge I gained from this research placement back to my home institute of Trinity College Dublin.
Why did you choose the host lab?
The aim of this research placement was to understand the role of PPAR proteins in NK cell metabolic and functional responses in obesity. I chose to travel to Dr Beyaz’s lab in Cold Spring Harbor because working in his lab provided a unique opportunity to achieve this goal. Dr Beyaz has done seminal work on obesity-induced cancer, facilitated in part by the multiple strains of PPAR knockout mice and cancer/obesity mouse models his lab has established. Over several Skype calls with Dr Beyaz, together we established clear goals for the 6 weeks I would spent in his lab. Cold Spring Harbor is a world leading scientific institute that ranked #1 in the world in terms of published paper citations. In addition, it has been the workplace of eight Nobel Laureates in the past 125 years. Therefore, this research placement was a unique opportunity to gain experience in establishing a new scientific collaboration with a leading expert in the field of cancer biology in a world-renowned scientific institute.
Can you summarise the research you did or what you learned on your visit?
The aim of my research placement was to understand the role of PPAR pathway activation in NK cells in obesity and to learn how to prepare samples for CHIP sequencing. I performed flow cytometry of blood-derived NK cells and found an important role for PPARα in NK cell maturation; PPARα deficient mice had ten-fold less numbers of circulating NK cells with reduced maturation mature expression compared to WT control mice. In addition, the effector functions of spleen derived NK cells from PPARα-/- mice were significantly enhanced following cytokine stimulation compared to WT NK cells. These findings are in line with our previous research, which shows that activation of PPARα/δ pathways reduces NK cell effector functions and mimics an obesity setting. During my 6 week placement I learnt how to prepare and process RNA samples for CHIPseq analysis. Gaining experience with this new technique will greatly enhance the calibre of research contributing to the publication of the PPAR findings thus far. Learning how to prepare samples for CHIPseq samples was also a valuable way to maintain collaborative relations with Dr Beyaz as we plan to send him CHIPseq samples in the future for sequencing.
It has benefited my home lab as we now have an ongoing collaboration with the Beyaz lab.
What were you able to do that you could not have achieved in your home lab?
This research placement was extremely beneficial on both a scientific and personal basis. There are currently no PPAR knockout mouse strains established in Ireland. Hence, the findings from the PPARα-/- experiments would otherwise not have been possible. CRISPR technologies, for the development of genetically modified mice, are a considerable financial and time-consuming investment. However, due to the promising preliminary findings from this placement, the Lynch lab has decided to invest in the development of a double PPARα/δ CRISPR knockout mouse in Trinity, which will be the first of its kind in Ireland. This will allow us to use the cancer and obesity mouse models we have established in the Lynch lab to further define the role of PPAR pathways in the obesity associated anti-cancer immune defect. In addition, learning how to prepare samples for CHIPseq sequencing has broadened my area of scientific expertise and will benefit not only my own project, but also that of my lab member’s projects in the future. Finally, establishing this new collaboration with a US based lab widened my scientific network and was of great personal benefit.
Did you take part in any interesting local/cultural activities?
I thoroughly enjoyed my time in the Cold Spring Harbor Laboratory. This research institute is one of the most picturesque in the world. Dr Beyaz’s lab overlooks the harbour itself, just meters from the water and surrounded by trees. Dr Beyaz was a fantastic scientific mentor, but he was almost equally as passionate about farming. During my visit, I helped him tend to his vegetable patch on the grounds of CSHL where he was growing watermelons, chillies, courgettes and tomatoes. The only downside to the farming was the bugs and mosquitos (which loved the taste of my ankles as much as I loved the taste of the fresh veggies they called home!) Cold Spring Harbour is just a one-hour train ride from New York City. I have always wanted to visit the big apple and so the weekends I spent in New York City were a personal highlight for me. I thoroughly enjoyed visiting the many tourist attractions such as the Brooklyn Bridge, the Statue of Liberty, Grand Central, Central Park, Ground Zero and Wall Street. I also visited Boston, which was 5 hours away, where I ran down the banks of the Charles River, read in the Boston common, went to an outdoor cinema and did the freedom trail walking tour.
Did you have a personal mentor or anyone who particularly helped you? Tell us about them.
Semir Beyaz was a very helpful mentor during my research placement. Dr Beyaz is a newly established Principal Investigator in CSHL who remains heavily involved in the bench side research. His passion as dedication for science is infectious. Due to his experience and expertise in epigenetic techniques, it was extremely beneficial to learn CHIPseq sample preparation directly from him. From this placement, I have learnt enough to allow me to establish this technique in Trinity, which will greatly benefit me personally and all member of my home lab.
Have you brought back any specific knowledge/technique that has benefited your home lab?
This EACR travel fellowship has given me the opportunity to learn and establish a new scientific technique in the Lynch lab. I now know how to prepare and process samples for CHIP sequencing analysis. This will benefit my home lab as one of the ongoing projects is identifying the impact of the diabetic drug metformin on the metabolism and function of Natural Killer cells in obesity. Using the knowledge and experience gained in Dr Beyaz’s lab in CSHL, I will teach my fellow lab members how to prepare samples for CHIPseq, which will allow them to understand the precise epigenetic changes that metformin induces on the NK cell epigenetic landscape. In addition, this EACR fellowship has established a collaborative relationship with the Beyaz lab. Dr Beyaz has kindly agreed to sequence RNA samples for us in the future.
How has this visit been beneficial to your research and/or your career?
This EACR travel fellowship has been invaluable on both a scientific and personal basis. It has allowed me to gain experience in a new scientific technique, in a world-leading research institute. It has broadened my area of scientific expertise, as well as my scientific network to the United States. In addition, my mind has been opened to the inner workings of a US based lab environment. Having been awarded this prestigious travel grant, my CV will undoubtedly be enhanced by displaying independently funded, international lab-based experience. It has benefited my home lab as we now have an ongoing collaboration with the Beyaz lab. Lastly, it has benefited me personally by broadening my horizons, giving me a sense of scientific independence and increasing my confidence for future grant applications.