CRDG: A year in review

A year ago today was the first official day of the Computational Rare Disease Genomics team at the Wellcome Centre for Human Genetics. Whilst 2020 wasn’t an ideal time to start a research group, I am very proud of what we have achieved in our first year. Today seems like a good time to share some of these successes and to reflect on being a new group leader in the midst of a global pandemic.

Building an awesome team

One of the scariest things I have found about being a new PI is recruitment. Starting a group is a perfect opportunity to set the tone and build an atmosphere that reflects the group you want to work in - for me, that was one that fosters kindness, teamwork, and collaboration. But for this to work, the whole team needs to share the same beliefs and values. I am incredibly fortunate to have had a group of amazing individuals pass through and/or start in the team over this past year!

The first arrival to the fresh new Slack was Jonny, an undergrad student in Biomedical Engineering at Imperial who was taking a break from his studies for a year. Jonny was officially part of the group for only three months at the end of 2020, but we refused to let him leave so he remained a regular at lab meetings until very recently. We have finally had to say goodbye (for now) as he starts a year-long internship at GSK (we will miss you!).

A week later we became four when we were joined by the incredible Alex, a postdoc with a background in evolutionary genetics (and only a tiny obsession with cats...), and CRDG’s first DPhil student✝, the super awesome Nechama (who has a lot(!) of siblings).

At the end of May we were very fortunate to have Fred join the group for the final rotation in the first year of his DPhil in Genomic Medicine and Statistics. Fred was only in the team officially for 10 weeks, but analysed so much data and created so many plots that he could only cram ~1/5th of them in his final project presentation!

Over the summer we had three undergraduate students join us for short projects - Megan, Ashley, and Shan. Although none of them had much prior coding experience, when they presented their results in a lab meeting at the end of their projects I was blown away by how far they had come in a few short weeks. We also have superstar clinician Esther with us part time wrestling with the Genomics England 100k data.

Whilst we have had a lot of short term lab members leave over the last few weeks, we also have two longer-term new arrivals just starting, or starting soon (pending visas). We are super excited to have Elston join the team as a Research Assistant (when he finally escapes the Australian lock-down) and Maria starting as our second postdoc very soon!

To all the team - thank you for keeping me sane, and helping me through the ups and downs of the past year. A special thanks to Alex and Nechama, the constants who have been absolute rocks throughout! Alex, you have an incredible skill of noticing when I have too much on my plate and delegating it to yourself, and Nechama, you are the queen of asking intelligent questions and starting thoughtful discussions.

The pandemic has prevented many of the team from ever meeting in person, but we have had regular ‘tea and chat’ sessions every Monday and Friday mornings to keep us feeling connected and help us get to know each other outside of science.

The team during a lab meeting on Zoom

The team during a lab meeting on Zoom

Successes in science

This year has seen a couple of follow-up papers to our initial work characterising upstream open reading frame (uORF) variants published. Firstly a description of our UTRannotator tool in Bioinformatics, led by the awesome Xiaolei Zhang (now a postdoc with Ewan Birney at EBI), and a super fun collaborative project with Caroline Wright looking at the impact of these variants in Developmental Disorders (see blog on this work here). This later project involved some really cool functional work through collaboration with Paul Barton and Nick Quaife at Imperial College London, and Enrique Lara-Pezzi and Laura Ramos-Hernandez at CNIC in Madrid.

Whilst a lot of our first year has been focussed on recruitment and team building, there has been some very exciting progress on the team’s main research projects. Stay tuned over the next few months for a tool to visualise the impact of 5’UTR variants on uORFs and an analysis of UTRs across and between gene-sets. We are also co-leading (with the brilliant Jamie Ellingford from the University of Manchester) the development of clinical guidelines for the interpretation of variants in non-coding regions of the genome. These guidelines are currently undergoing testing and we hope to release them for wider review by the community in late Autumn.

Finally, we are incredibly excited to have approval for a new project using the UK Biobank to study some common neurological phenotypes. This is a topic that is very close to my heart and involves a new collaboration spanning the Atlantic - I can’t wait to get started on this one!

Looking ahead to year two

A lot of the first year (or more) of setting up a group is laying the groundwork so both the team and the science can then flourish over the years to come. I am really excited to see what the next year will bring. In particular, I am hoping that we can interact more in person. This should become easier as four of the new and existing team members all move to Oxford before the end of the year (from as far afield as Australia). I never imagined I would only be in Oxford twice in a full year! I am hoping we can also settle into more fun and exciting science and build more collaborations locally around Oxford. Finally, we are keeping our fingers tightly crossed for the outcome of a couple of grant applications...

Reflection - starting a research group in a pandemic

Finally, I thought it worth reflecting a little bit on what it has been like setting up a new research team in the middle of a pandemic. This is in part as solidarity with anyone else who has been going through the same thing over the last eighteen months, but I also imagine much of this is generic to all new group leaders.

Being a new PI is known to be a lonely space - you are plunged into the deep end and mostly left to work things out for yourself. This, I think, is magnified 10-fold when having to work entirely from home. It is very hard to make new connections or to figure out who everybody is from an office 60 miles away. Even the smallest issues that could be solved by a quick knock on someone’s door take a chain of emails to resolve. And in a world where everyone is plagued by a calendar full of Zoom calls there is a huge amount of guilt around suggesting someone add another ‘just for a chat to say hello’. I have felt enormous gratitude to everyone who has reached out to suggest a quick chat. I am also hugely fortunate to have a wonderful network of support around me - special thanks to the incredible trio of Cecilia Lindgren, Luke Jostins-Dean, and John Todd for always being there to answer any of my many questions and give their wonderful support and advice! Also thank you to the UK New PI Slack community - the camaraderie of the group and collective desire to support and uplift others is truly amazing.

So what have I learnt about being a PI and growing a team over the last year? Here are just a few thoughts:

  1. A large support network is crucial - both people locally on the ground, but also peers in other fields who are facing the same challenges.

  2. Adapting from a postdoc role of focussing on a single project for an entire day to having to switch between tasks every half an hour is something I have found quite challenging. A solution that has worked well for me is blocking ‘meeting free’ sections of my calendar to concentrate on bigger tasks (although this does require lots of back-to-back meetings at other times).

  3. I am a planner. And one thing this year has definitely taught me is that some things just aren’t plannable - take a global pandemic for instance. Multiple members of the team have had toddlers in and out of childcare, friends and family seriously ill, and periods of self isolation. The most important thing in these situations is kindness - being kind to yourself and to others, and encouraging others to do the same.

  4. I am slowly learning the valuable skills of learning to say no and not feel terribly guilty for doing so.

  5. It is easy to build a wall to live behind, but especially in times of isolation and anxiety, honesty and vulnerability are two incredibly important traits for building relationships and leading a team.

Finally, I don’t think any grant management system should give you a percentage on how far through a grant you are - how on earth am I already 20% of the way through my Henry Dale Fellowship? (queue endless screaming) Jokes aside, despite there being obvious challenges, it has been a really fun year and I am looking forward to many more to come!

✝ Another learning curve has been getting used to the Oxford language. A DPhil is a PhD to most people.

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DPhil student Nechama wins prize

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Non-coding region variants have an important role in developmental disorders