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October is Black History Month, which is celebrated nationwide every year to recognise the contributions that people from BAME backgrounds have made to this country. Here at DPAG, we get to know one of our Researchers - Pavandeep Rai, a Postdoctoral Research Scientist working in the Wade-Martins Group. Pavandeep is working at the forefront of an industry/academia collaborative project aimed at developing potential new drugs to treat Parkinson’s.

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What led you to a career in research?

I had a very good biology teacher at secondary school who was very passionate and helped me enjoy science. From there, I started learning about pathways in science and was fascinated by all the complex and interconnected issues, where if one very small thing goes wrong, it can affect the whole system. I wanted to problem solve how we can change things that happen to us.

Tell us about your research journey so far

I studied Biochemistry as an undergraduate at the University of Birmingham, and during that time I did a sandwich year at Alderley Park near Manchester working on mitochondrial toxicity. I loved working in a big company, and for a lab that was at a late stage of developing drugs that would soon go to patients. I also loved researching mitochondria - these are small entities in your cells producing the energy you need to survive, so any kind of disease affecting mitochondria causes you to produce less energy. They have the potential to affect all of your organs, but they mainly affect the brain. So, afterwards I decided to do a PhD with the aim of going into something drug discovery related. I first conducted an MRes in mitochondrial biology at the Wellcome Trust Centre for Mitochondrial Research at Newcastle University, then a PhD sponsored by Novartis screening compounds that may improve mitochondrial activity in mitochondrial disease. While I really enjoyed it, I found that mitochondrial disease is quite a niche subject area. I wanted to stay within drug discovery but apply my knowledge to a different field, and then my postdoc came up in Richard Wade-Martins’ lab. Mitochondria are affected in many other diseases, and one of those is Parkinson’s, so my postdoc involves using my knowledge of mitochondria drug discovery in Parkinson’s, and alongside that learning a new technique - the CRISPR-Cas9 gene editing system.

Why did you decide to research Parkinson’s?

All neurodegenerative diseases are going to become more prevalent with an ageing population. Parkinson’s is particularly interesting because it has a multi-faceted pathology - there’s so many different factors that can lead to Parkinson’s disease and such scope for research. It’s an incredibly debilitating disease and the current methods of treating it do not work well long term. We need to get a handle on it, the sooner the better. Also, its relation to mitochondria is just a very small proportion of it, there’s a whole breadth of research going on that I had no idea about before.

What does your project entail?

Celgene and Oxford University have come together to employ several people to really go through the life cycle of the compounds that could alleviate Parkinson’s. I am at the very forefront of that. I conduct genetic screening using CRISPR-Cas technology to find new targets that perhaps haven’t been considered before. It’s about trying to cure the underlying symptoms or identifying potential disease-causing genes to target. Have I found a new treatment target? Or is this a really interesting new gene to research further? It’s very discovery based.

What does your typical day at work look like?

I like to start early and get as much tissue culture done as possible – I grow a lot of cell lines for my work, so I’ll typically be in tissue culture until lunchtime (some weeks this may be all day). Then I like to use the microscope or conduct experiments in the afternoon. I try and take one day off a week to do admin and analysis work. My lab is really communicative, so we have 2 or 3 lab meetings a week to discuss our science, which is really important. They’re lovely bunch of highly collaborative and friendly people, we even run a British Bake-Off style competition every year! I also get the opportunity to work in multiple departments, such as the Dunn School of Pathology. I’m very lucky that my project involves a lot of different techniques, so I get a lot of variety in my day.

What do you most enjoy about your work?

I love looking at data and theorising what is potentially going on. I also love speaking to other scientists and coming up with new ideas and experiments. The trouble shooting is really frustrating, but once you get an experiment to work, that’s really rewarding. Say if you’ve been working on an experiment for months and it isn’t working, you’ve tweaked every single parameter and finally you get results you can use! I also enjoy collaborating with people across different field and disciplines, and attending conferences to learn about work being carried out at the forefront of science.

What’s the highlight of your career so far?

I just love working on the forefront of research, especially as CRISPR gene editing is so up and coming. The technology is moving so rapidly, I’m excited to see what will happen in the future and be a part of that. I can imagine what it must have been like for Bill Gates when computers were first coming out, because I feel CRISPR-Cas is going to be like that for healthcare in the future, easily within our lifetime.

What would you say is the next big step in Parkinson’s research?

The CRISPR-Cas field will make a huge difference. For example, I recently attended a Cold Spring Harbour conference where they demonstrated base editing. CRISPR-Cas works by cutting out the piece of DNA you don’t want. With base editing; instead of cutting it out and waiting for the cell’s repair mechanisms to fix that, you just go in and switch out the base that’s wrong. If you have one base in your DNA code that’s causing the problem, you can just replace it. So one step will be elucidating more gene targets in Parkinson’s using CRISPR cas screens. The second step will be using gene therapy methods to potentially target the underlying DNA defects.

What challenges have you faced in your career?

The biggest challenge for me is proving my output because science is quite archaic in the sense that if you don’t produce papers, it can be hard to secure funding. I’ve always worked in a field where I’m hindered by a company’s intellectual property and non-disclosure agreements, so while I’m doing valid work, I have very little to show for it in the way that academic science wants me to show progress and output. You need to have papers out there because that’s the main currency. I’d like to see a move away from that, so commercial collaborations are recognised, but how do we quantify that? If I carry on working for companies in academia, could I establish my own collaborations? I’m really enjoying my work, but I’m realising it might limit me in some way. Industry/academic collaborations are becoming more common now, so the idea of measuring outputs is going to become more of a relevant question.

What would be your next step in your career?

I’d still like to work in the commercial aspect of science, so this bridge between industry and academia. I like the freedom of academia, but I like the intentions of drug development and the scope it gives you to make more of an impact further along. But, I’m only a year into this postdoc, so who knows. I love drug discovery and I’d like to lead my own research one day, whether I go into industry or continue with industry/academic collaboration, I’m seeing how it goes. I love learning new techniques and being at the forefront of that work.

What new techniques and skills would you like to pick up?

CRISPR is a big one for me - I’d like to continue developing that work and pushing the technology as much as it can go. I’m also interested in understanding the commercial aspect of how research works within a pharmaceutical company setting, because that can massively affect how you approach your work. Although it’s not completely research orientated, it’s relevant to the progress of research in science and where you can make impact.

Have you been involved in any Public Engagement with Research?

When I was at Newcastle, I established a collaboration between my department and the Fine Art department. We funded 7 artists to shadow scientists and produce installations. We then exhibited their artwork and invited patients, researchers and the public to view it. It brought together people from all sorts of different areas - social sciences, arts and medical research. Although I’ve left, it’s still continuing - they now have funding to produce work for a conference that will demonstrate the interpretation of science through a more creative lens and make it more accessible to the public.

During my PhD, I had a good working relationship with one of the fine art students. We were involved in the National Trust’s Women in STEM programme last year, at a property called Cragside. We produced 3 6-foot wooden sculptures telling the story of mitochondrial donation and the effect mitochondrial disease can have on the body. They were really successful - they’re now displayed at a property in Northumberland called Cheeseburn.

Thinking about Black History Month, did you have any BAME role models growing up?

There were very few I can remember seeing outwardly, especially in science. I didn’t know anyone in my family or in the media. When you’re growing up in the 90s, the media is one of your biggest ways to consume information and it just wasn’t very prevalent. It’s important that we have more role models for different careers, and to make it more relatable for kids from different ethnic backgrounds to even consider those career choices. I don’t think they necessarily would if they can’t see themselves represented or place themselves in those shoes. I don’t think this would take away from anyone else’s experience, in fact I think it would enhance them to show lots of different faces in different areas of our lives that reflects the greater world.

What would you like to see more of to help facilitate this?

I think you need to start really early. You need those role models in place when kids are quite young, as you have to make so many of your decisions when you’re doing your GCSES. As young as 14, you have to think about your A levels, and what A levels you do dictates your degree. I think the media has a great role in that. Social media has massively increased representation, but I think that can be pushed more. It’s also important to reach people who aren’t in the scientific community – we know that science is quite diverse internationally, but I don’t know if that’s put across very well to people who aren’t in the science sector. I would like to see the scientific community using different avenues to take science to the audiences that would not necessarily come across it in their day-to-day lives.