Rushad Pavri has been a group leader at the IMP since 2013, conducting innovative research that reinforced the IMP’s expertise in immunology and genome biology. At the end of this year, he will be moving his lab to King’s College London to continue his research on the molecular mechanisms of antibody maturation and genome instability. Once again,our interview series switches perspectives from job seekers to a recruiter, as Rushad will be looking to hire new lab members, including a postdoc and a PhD student.
What is your current research about?
There are two main lines of research my lab has been exploring. The first is antibody maturation, an umbrella term for processes that diversify antibodies when B cells encounter foreign antigens. We previously worked towards understanding the mechanism of class switch recombination, through which various classes (isotypes) of antibodies are produced. We made some unexpected discoveries, for example, that DNA replication is required for class switching and that transcription was required for super-enhancer function. More recently, we used high-resolution genomics to show how 3D chromatin architecture regulates class switching. In recent years, we have shifted our attention to the other critical process in antibody maturation, somatic hypermutation, which introduces mutations into the antibody variable regions, creating a wide array of antibodies capable of binding the billions of different antigens our bodies encounter. We have developed new assay systems to study somatic hypermutation, identified new factors using CRISPR screens, and developed tools to study various aspects of the mechanism.
The second area of focus in the lab has been towards understanding the molecular mechanisms regulating the genesis of chromosomal translocations that result from the antibody maturation pathways and which are associated with various B cell lymphomas. Our study uncovered an unexpectedly critical role for DNA replication timing in regulating these translocations. It was the first time that replication timing had been directly implicated in any kind of translocation.
How is your move to King’s College London going to affect your research?
The lab will be embedded in an environment that features research in immunology, autoimmune diseases, and infectious diseases and I have already been discussing collaborative projects on topics that are new to me, which is always exciting! King’s is a large campus that hosts a major hospital (Guy’s and St. Thomas) with a lot of clinician scientists. Here too, I see a lot of potential for collaboration given the access we will have to human tissue samples that will allow us to explore new questions.
What’s next for your lab?
We will focus much of our effort on studying the mechanism of somatic hypermutation. Firstly, we will be studying the role of some of the new factors we identified from our CRISPR screens using in vitro model systems and transgenic mouse models. We have no idea what they do in the mutational process and it’s going to be an exciting venture to figure it out.
A second problem we’ve started tackling is the role of long-range genetic interactions in antibody maturation. Both class switching and somatic hypermutation rely on genetic enhancers – regulatory DNA sequences located hundreds of kilobases away from antibody-encoding genes. Since regulation happens over such long distances, it’s obvious that chromatin folding is involved: the whole structure must bend to bring the relevant sections close together. Once we’ve moved to London, I’d like to keep exploring how genome architecture influences somatic hypermutation and class switch recombination.
And as a third step, I’d really like to pin down the rules of the mutation mechanism in somatic hypermutation. These mutations don’t seem to be predictable from their sequence. We know that the enzyme that makes them happen has certain preferences, but the exact rules and the role of the local sequence context are very unclear. So, this will also be a key project for the future.
What’s your lab philosophy?
I’m a very hands-off supervisor and I don’t like micromanaging people. I have an open-door policy: my lab members can ask me for advice or help whenever they need to. However, I generally trust them to handle their projects and work through the difficulties themselves because overcoming those hurdles is what builds not only their technical skills, but more importantly, their self-confidence. This is critical for their scientific and personal maturity. In fact, watching this scientific maturity unfold over years of training is one of the most rewarding and satisfying feelings I have experienced! I also strongly encourage collaboration between lab members: it’s very much about helping each other, so that the lab benefits as a whole.
What kind of positions will be available once you move to London?
I have a postdoc position advertised online as well as a PhD student position, which is available through the King’s PhD programme. The latter works via a process similar to the Vienna BioCenter PhD Program.
What’s one skill you want your lab members to learn?
If I had to pick one, I’d choose time and resource management which are essential for success. To me, this means not only careful planning of experiments, but also involves getting work done in a reasonable time. I find that this is not only important to achieve good mental and physical health, but it also benefits your research as a rested mind works best when solving problems.
What do you expect from your lab members?
First and foremost, I expect lab members to have passion and high motivation for what they do – loving what you do is vital, because only then can you overcome the many hurdles and frustrations of research. Working at the boundary of knowledge involves unpredictable outcomes and setbacks: bouncing back and finding alternative solutions are what makes research exciting. In addition, I’d like all my lab members to have an affinity for collaboration and open communication. Collaborations are mutually beneficial when conducted in a transparent manner, and a good collaboration requires direct and open communication. I've learned so much from collaborating with colleagues on campus and abroad. Finally, I encourage people to talk to me directly if there are problems, either scientific or personal, because the sooner these are resolved the better it is for everyone.
Why should applicants consider King’s College London?
King’s hosts a vibrant and highly collaborative community of scientists with a diverse array of research interests, both fundamental and clinical/translational. All state-of-the-art facilities are available. Moreover, you’ll be in central London: we’re located just off the Thames River at London Bridge. Therefore, you’ll be very close to other major universities and institutes such as the Crick, Imperial College and UCL. This means you’re never far away from an expert in pretty much any scientific topic and cross-collaborations between these institutions are very common and strongly encouraged. All of these factors make London a major global hub of scientific excellence. In addition, as is well-known, London is a vibrant, colourful and multicultural city. No matter what your interests or hobbies, you’re sure to find high-quality stuff in London!
Interested in applying as a postdoc? Click here
Interested in a PhD with Rushad Pavri? Apply through the PhD programmes at King’s College London.
You can contact Rushad Pavri at rushad.pavri[at]imp.ac.at.