Moments before thesis submission...

Lab retreat 2024

Congratulations Dr Ntombizodwa Makuyana!

Congratulations Dr Ntombizodwa Makuyana! Our 24th PhD completion from the lab, and our 1st Cambridge PhD defence! Way to go Tombi! 

Designer IL2 mutations for clinical use

We have a new pre-print out, on novel designer IL2 mutations!

IL2 is a powerful immunomodulator, but the dual roles make it complex to use, and many designer mutations reduce bioactivity or result in poor production. This makes it much harder to move these muteins to the clinic.

Rob van der Kant, Joost Schymkowitz and Frederic Rousseau from the VIB Switch lab took up the challenge of designing new IL2 mutants that not only improve the specificity for Tregs or CD8 T cells, but also maintain bioactivity and actually improve production capacity. They sent the designs over to us to test!

Great work from Amy Dashwood screened these mutations designs in vitro, with in vivo testing by Ntombizodwa Makuyana resulting in a set of mouse and human IL2 muteins with the desired biological properties. In particular we solve some of the common issues with IL2 muteins by considering the bound and unbound structures. For example, to make IL2 specific for Tregs, the approach is to allow binding to IL2RA, the high affinity receptor sub-unit used by Tregs, while block binding to the IL2RB used by CD8 T cells. The problem is that Tregs also need the full IL2RA-IL2RB-IL2RG trimer to assemble for optimal signal. So the typical Treg mutein is more specific, but also has poorer bioactivity. We solved this by creating a block between IL2 and IL2RB that moves out of the way after IL2 binds IL2RA, allowing the full trimer to form. These muteins are not only superior to the original IL2 in terms of cellular specificity, but by removing the aggregation-prone regions. By identifiying the aggregation gateway residues and changing them to be aggregation-resistant, we can further improve these muteins by making them aggregation resistance. The net effect is that the IL2 muteins we made are more specific for either Tregs or CD8 T cells, and will also be cheaper and easier to produce - the perfect combo for biologic drugs!

Our take-home message: if you are engineering proteins for therapeutic use, remember to take into account production, aggregation and bioactivity. These factors count when it comes to making a drug!

Take a look at the full paper on BioRxiv.

Lab Gantt chart

Our lab Gantt chart, modelled by current undergraduate interns Ray Yan and Preesha Jain! It covers 185 lab members, based in VIB and KU Leuven in Belgium, and the Babraham Institute and University of Cambridge in the UK. An average of 14 team members joining annually in Belgium (largely because of the fantastic Erasmus program allowing mobility across Europe!) and 8 team members joining annually in the UK. Median duration of 12 month stay in Belgium (with Masters students being the median lab member) and 18 month stay in the UK (with PhD students being the median lab member, but none yet to graduate!). A whole lot of memories and nostalgia in this picture!

Lab photo

The Golden Pipette

Science plays the long game, but Adrian Liston celebrates the small achievements his team makes along the way. 

Danielle Gerhard, PhD, writing for The Scientist

Hanging on the wall of immunologist Adrian Liston's laboratory at the University of Cambridge is a commemorative plaque. Engraved are the names of laboratory members who received the Golden Pipette Award, an annual honor that recognizes incremental advancements and team players. It may or may not grant the recipient the Midas Touch, but Liston reflected on how the tradition fosters a sense of community.

What is the Golden Pipette origin story?

In 2016, we had a special PhD candidate graduating from the lab. James Dooley had been a technician in my lab for several years prior to his graduation. To celebrate his achievements and the impact he had on the careers of others in the team, we painted one of his pipettes gold. The gesture was well received, so each year, we award the pipette to an individual who made a significant contribution to the team.

What does the Golden Pipette represent?

Science is tough. We work at the very limits of human knowledge, which means we constantly fail. The Golden Pipette tradition is one of the ways we create a positive culture and supportive environment. Big achievements, such as a paper, take a long time, so it’s important to celebrate the small successes: generating a transgenic mouse; developing a new protocol; the heroic effort that ends up as supplementary figure 12. It also signals our values and priorities: imagination, creativity, robust science, and team contributions. 

How did your team respond to the Golden Pipette?

It seemed silly at first, but the tradition has outlasted everyone in the group. It serves as a visual reminder that we’re part of a greater project. In a recent hiring round, several people said that they look forward to the chance of winning the Golden Pipette.

Read the story as told in The Scientist...

Becoming a Scientist: The Graphic Novel

Our latest project has just been released: Becoming a Scientist: The Graphic Novel!

The novel follows the stories of the amazing team members in the lab (or, at least, those team members who have been around since last October when we started this project!). We follow their story in becoming a scientist: the barriers they had to overcome, the role-models who helped them on the way, and the motivation that drove them to enter STEM.

This is a unique project for us, because it isn't about our science. It is about us as scientists. Where we came from, and how we got here. None of us were destined for science, yet somehow here we are, working together to better the world...

Our amazing illustrator, Yulia Lapko, brings to life each person's story. We have Magda, daughter of Somali refugees, drawing strength from her mother's sacrifice and equally determined to help others in turn. We have Alvaro, who barely managed to get into school growing up in Peru, and has now made it to Cambridge with a ripper of an under-graduate project. James, who took a long and winding route, overcoming every disadvantage life gives a foster kid, and yet somehow beating the odds and now helping others succeed. Stevi made the transition from patient to researcher, and Tombi brings her mission from Zimbabwe to help the global ubuntu. I realised, looking around the lab, that I could talk about how inspiring I find literally every person - so I put them all into a book!

I draw inspiration from these amazing team members. I could have written this story at any point over the past fifteen years - we have nearly 200 amazing alumni, each with their own unique story. I wrote these stories to provide role-models to anyone thinking about starting a career in science. Science is not for the privileged few. Science is for anyone who has ever asked "why?", and anyone who is too stubborn to know when to stop asking! Take a look into these stories - if we can succeed in science, you can too!

The book is live now to read at Issuu, and will be released soon in print. If you want to support more innovative projects in broadening participation from our lab, drop us a donation!

In the news

The Cambridge Independent