Boehringer Ingelheim Fonds to support protein degradation research
Lillie Bell joined the IMP in 2022 through the Vienna BioCenter PhD Program. In the lab of Tim Clausen, she is investigating the regulation of a giant enzyme that helps rid the cell of unwanted pathogens, the E3 ligase RNF213. The Boehringer Ingelheim Fonds (BIF) will now support her research with a PhD Fellowship for the next two years.
Where did you study before joining the Vienna BioCenter PhD Program with the IMP?
I received my bachelor's degree in biochemistry at the University of Leeds. During my undergraduate time, I did a year in industry at AstraZeneca. This was during the pandemic, which was good timing, because it meant I could still work during lockdowns. There, I worked in high throughput screening looking for molecular glues.
Is that where you discovered the world of protein degradation?
Yes. We were researching E3 ligases – big enzymes that tag unwanted proteins for degradation with ubiquitin. The idea was to find synthetic compounds that were specific for one E3 ligase, which we could tether to neo-substrates and target for degradation, even if they weren’t natural substrates of that E3 ligase.
How did you get to know Tim Clausen’s research?
Once I was back at university, I worked on a structural biology project linked to ubiquitin. There’s a famous symposium in the field, called the Ubiquitin & Friends Symposium, with an associated website. The participating labs were advertised there, and Tim’s research seemed very appealing. He was recruiting a student at the time, so I applied to join the Vienna BioCenter PhD Program.
What is the project that the BIF fellowship will support?
I’m working on a giant E3 ligase called RNF213, which is involved in innate immune defence. It can co-localise with pathogens and directly ubiquitinate them to flag them for degradation. The goal of my project is to understand the regulation mechanisms of RNF213 – it’s a complex enzyme, with a ligase function and an ATPase module.
Do you collaborate with immunologists at the IMP?
I definitely benefit from their expertise. I’m particularly grateful to have immunologists in my cohort – some in the lab of Moritz Gaidt. They specialise in innate immunity and have much more expertise in cellular biology than I do. We ask each other a lot of questions to reach our research goals, and it’s been very helpful. That’s a huge strength of the Vienna BioCenter PhD Program: you start your doctoral journey with a supportive group of students with a wide range of expertise, who also end up being your friends. I think this is particularly important for someone who has never lived abroad like me.
What else will BIF help you with?
The BIF gives me another cohort, so to speak. All fellows in one selection get to be in touch with each other and participate in a conference to present their projects. This is a great opportunity for networking among BIF fellows.
How were your first steps into your doctoral studies?
I was overwhelmingly scared about starting – I had little hands-on experience in the lab in comparison to other students. And yet I quickly managed to catch up, because there’s always someone to help you through technical difficulties. I’m now in a very exciting phase of my project, where I can come up with ideas to push my research forward and make it happen. I’m pleasantly surprised by how excited I am.