In this article, BSI member Dr Simone Webb shares her experience conducting a lab placement in the Memorial Sloan Kettering Cancer Centre in New York, USA, in summer 2023 with the support of a BSI Career Enhancing Grant.
Poised for challenge
Our immune system is an evolutionarily conserved network of cells that are crucial to protect us from infection. Immune cells first emerge in early embryonic development, though our understanding of their migration, communication and differentiation into mature and functional components of the immune system is incomplete. Single-cell genomics technologies now allow us to access molecular profiles of tissues, including gene and protein signatures, at unprecedented cellular resolution.
I completed my PhD research with Professor Muzlifah Haniffa at Newcastle University, who is a clinician scientist, co-lead of the Human Cell Atlas Developmental bionetwork and Academy Medical Sciences Fellow. The Human Cell Atlas is an international consortium which aims to map all single cells in the human body across all ages and in health and disease. Much of my PhD research focused on developmental immunology, where I analysed single cells from precious prenatal tissues using tissue biobanks such as the Human Developmental Biology Resource. This work revealed a prenatal immune system poised for challenge, with implications in the therapeutic use of immune stem cells and to regenerative medicine.
Expanding the technical toolkit
My postdoctoral research builds on my background in exploring the foundations of the immune system, and now expands into all bodily systems present in early embryogenesis. We are interested in expanding the technical toolkit used in this project, since we are now able to assess single cells using epigenomic modalities, in addition to the RNA and protein epitope data my previous research has focused on. This began my journey into learning single-cell multiomic data analysis, and better appreciation of the biological questions we might be able to answer when assessing chromatin accessibility data.
With the support of a BSI Career Enhancing Grant, I was able to complete a three-week placement at Professor Dana Pe’er’s lab at Memorial Sloan Kettering Cancer Centre in New York. Dana is a pioneer in computational and systems biology, and Howard Hughes Medical Institute Investigator. Dana’s lab regularly develops new algorithms and computational tools for single-cell data analysis, and places challenging and clinically relevant biological questions at the core of their research. Especially relevant for my research project, Dana’s team have innovated to overcome the issue of sparsity in single-cell chromatin accessibility data through use of a metacell inference algorithm.
Multiomic data analysis pipelines are still being carved out, and some issues such as sparsity have not yet been resolved to the extent of significant community endorsement. It was therefore exciting that while discussing research projects during a virtual call with Muzlifah and Dana, Dana kindly extended the offer of hosting me for a lab placement. This BSI grant was advertised a few short weeks later, and both Muzz and Dana were extremely supportive in putting the application together.
Computational techniques in New York
I arrived in New York in mid-June, and as I was only able to visit for three weeks, we decided to select a high-quality subset of our Haniffa lab embryo data to trial run through the Pe’er lab’s general multiome analysis pipeline. Although this process could have been completed remotely, having access to this welcoming and engaged computational team meant my deeper understanding of each analysis step was massively accelerated through daily face-to-face discussions of pitfalls, recommended tweaks to the workflow, and pointers to additional resources. Crucially, I achieved a much greater understanding of how their current multiome analysis approach fits into the wider single-cell multiome analysis tool ecosystem, and how I might adapt this approach for my future purposes.
In addition to the practical analysis steps learnt during this lab placement, there was also a lot to be learnt by being in this different research environment. Having worked within the Haniffa Lab for both my PhD and postdoc, I was keen to see how time in a majority-computational research environment might differ, and what I could take away from this experience in terms of coding and general research practices. I enjoyed the time I was able to use to reflect on my coding during this placement, which was partly due to my physically being away from the daily responsibilities of my team, but also due to being around coders day in and day out. I also found it interesting to meet and learn of the work of the Single Cell Analytics Innovation Laboratory team at MSK, who sat right alongside Dana’s team, many of whom helped me daily, and gave me an appreciation for the different mechanisms through which a computational research team can be supported. This made me consider the role of the parallel teams we have in my home institutes (Newcastle University and Sanger Institute), and the shared values that make these innovative facilities work well.
These new perspectives on protected coding/research time, and mechanisms for lab support gave me a lot of food for thought regarding future research and fellowship applications, which I brought back to my PI and wider team, and which formed the basis of a very interesting reflective team discussion.
The BSI Career Enhancing Grant allowed me to visit and learn from a world-leading computational biology group and begin to develop key analytical skills in the field of single-cell multiomic analysis. I would like to thank Professor Dana Pe’er for allowing me to join her research team over the summer and encouraging me to build bridges to make the most out of my short time. Thanks to the wider Pe’er lab for being so welcoming, instructive, and open to sharing their expertise and experiences. I would also like to thank my PI Professor Muzlifah Haniffa for allowing me to focus this time on skills training with no condition, and to the British Society for Immunology for funding this lab visit, which has been invaluable for increasing the impact and scope of my postdoctoral project.
It is an exciting time to work on developmental and human immunology, and the opportunity to train in one of the most exciting analysis tools out there was one which I am very grateful for, and which I am sure will elevate the impact of my future work.
Dr Simone Webb,
University of Newcastle and Sanger Institute