Image credit: Wellcome Sanger Institute
As early career scientists, postdoctoral researchers at the Wellcome Sanger Institute are pushing the boundaries of knowledge and driving our world-leading research. They are also training to be the next generation of leaders in genomics.
In 2022, supported by our postdoctoral committee, a new internal funding scheme for the postdoc community was launched. The aim was to accelerate postdocs along their career trajectory by familiarising them with grant application processes and helping them develop a track record of competing for independent funding.
Here, the first two winners of the Accelerator Award tell us about their work and life at Sanger.
Matt was awarded £8,500 for a research visit to the Cancer Research UK Cambridge Institute.
Matt completed his PhD in cancer immunology at the Francis Crick Institute. He spent his first Postdoc role at Astra Zeneca with a translational focus on oncology and therapeutic genome editing. Matt then joined Sanger for his second Postdoc role in January 2020, where he now works on dissecting the response and resistance to cancer immunotherapies using systematic, functional genomics approaches.
Matt’s ambition is to develop an independent research programme using CRISPR technologies to investigate the role of gene variants in cancer progression and response to therapy.
About the project:
Lethal cancers invariably evade destruction by the host immune system. Cancer immunotherapies are drugs that can re-stimulate the immune-mediated destruction of cancers, causing durable responses in some patients. However, not all patients respond to these drugs, making combination strategies an appealing option for improving patient outcomes. The Garnett lab has produced large-scale, unbiased datasets that have unexpectedly revealed that certain genes in cancer cells can drive resistance to immune attack.
Enabled by funding provided by the Accelerator Awards, Matt plans to test whether inactivation of such genes increases sensitivity of cancers to immunotherapy. To do so, he will develop a new collaboration with the Cancer Research UK Cambridge Institute. By spending some time in the lab of CRUK Group Leader, Tim Halim, Matt will be able to deliver a pilot project employing translationally-relevant mouse models of cancer to test whether these genes are promising drug targets for combination treatments with cancer immunotherapies. Inhibitors to one of the lead targets have already been developed, so there is a potential for rapid translation of the findings to a clinical setting.
The Award will enable a project that could not be performed by either institution in isolation. It will facilitate animal studies not possible at Sanger, as well as the transfer of knowledge and technical skills between the two institutes.
“The application was very similar in structure and process to other research grants, so this was a very valuable experience for me as a Postdoc. I got really useful feedback from the interview panel, which I have learnt from, and hopefully this will increase my chances of success for other grant applications in the future.”
Dr Matt Coelho
Jimmy was awarded £5,000 for a research visit to the Institute for Computational Biology in Munich.
Jimmy did his PhD at the University of Hong Kong where he explored novel metabolic hormones in fat-liver cross talk and their implications in the treatment of metabolic diseases. Jimmy moved to Sanger for his first Postdoc in 2018, joining the Hemberg Group to develop his computational skills. During this time, he developed “Scfind” - an interactive open-source R package for single-cell data analysis. Now in his second Postdoc role, in the Bayraktar Group, Jimmy performs spatial transcriptomic analysis of end stage COVID-19 and spatial and single-nucleus analyses of cells involved in human development.
In the future, Jimmy aims to build an independent research programme that uses leading-edge computing approaches and large-scale genomic sequencing data to improve human health.
About the project:
Jimmy plans to generate a reference “street map” of the brain to support the early diagnosis and treatment of motor neurodevelopmental disorders, such as ADHD.
The primary motor cortex (M1) is a centre in the brain that plans and executes voluntary movements. In humans, the structure of the superficial-, mid-, and deep-layers within brain cortex are easily recognisable under a microscope. The organisation of cellular architecture in M1 is distinct from those of regions responsible for other brain functions. During foetal development and soon after birth, this architecture serves as a scaffold for precisely coordinating the paths (connections) between the brain fibres that span the different M1 layers and that are responsible for conveying the signals that result in voluntary movement. However, little is known about the mechanisms that inform path development and thus what goes wrong to result in disrupted signals.
To develop understanding of the mechanisms at play, Jimmy will profile gene expression in every cell and take very high-resolution snapshots of the M1 region at different time points of early human development. By undertaking a research visit to the lab of Fabian Theis in Munich, Jimmy will equip himself with skills that will enable him to develop Artificial Intelligence methods. These will allow his data to be combined so that he can study how brain cells coordinate with each other over space and time. Jimmy will then be able to create his “street map” of dynamically changing communication signals across multiple layers, to better understand the navigation of brain fibre connections over long distances.
“This Award will be a critical step towards fulfilling my professional aspirations. Conducting research in the Theis lab allows me to combine my experimental and computational modelling expertise, creating a pilot study that I can use to acquire further funding in the future.”
Dr Jimmy Lee