Rebecca Wadey
Cardiff University & AstraZeneca

Devon Shannon
Exeter University & GlaxoSmithKline

https://doi.org/10.36866/pn.92.34

Rebecca Wadey, Cardiff University & AstraZeneca

What are you studying and what led you to this?

I am currently studying for my PhD entitled ‘Validation of Translational Biomarkers of Renal Injury’ at Cardiff University. It’s a four-year, BBSRC funded Industrial CASE studentship with AstraZeneca. Prior to starting my PhD, I did a Biomedical Sciences BSc degree at King’s College London. My first exposure to working in a lab was during my third year placement with Cathy Shanahan studying vascular calcification. I really enjoyed my placement in her lab and decided to do a research based masters after I graduated – that’s what brought me to Cardiff! I worked in Sarah Hall’s lab for the year studying the control of cardiac myocyte cell volume and then got my PhD studentship in Daniela Riccardi’s lab just down the corridor!

How did you come to do a placement at AstraZeneca?

Students with the Industrial CASE studentship have to spend a minimum of three months on placement with the industrial partner, and in my case this was AstraZeneca. AstraZeneca is a multinational biopharmaceutical company with a large research and development site in Cheshire, and I moved there for the duration of my placement. Although my placement was a requirement for completion of my PhD, I went there as they had access to equipment and samples that were not available to me in Cardiff.

What are you doing there?

My PhD centres on the validation of novel biomarkers of drug-induced acute kidney injury. Currently, a diagnosis of acute kidney injury is made by either histopathological examination, which requires an invasive biopsy in humans and which is a terminal procedure in preclinical species, or by monitoring changes in serum creatinine and blood urea nitrogen, parameters which change when kidney function declines. The problem with serum creatinine and blood urea nitrogen is that they are very insensitive and non-specific and therefore an extremely large amount of kidney injury has to occur before changes are seen.

I went to AstraZeneca to help validate some of the novel biomarkers of kidney injury that have recently been identified. Ideal biomarkers should identify injury early, localise the site of injury, reflect the degree of injury and be present in urine so that they can be tested for using a dipstick. In addition, ideal biomarkers should be applicable to both preclinical species and humans. I carried out immunohistochemistry for six biomarkers on kidney tissue obtained from rats which had been treated with Cisplatin, an anti-cancer drug with a known nephrotoxic side effect, and correlated tissue expression with urinary presence, and the work that I did on my placement has recently been published! [Wadey RM, Pinches MG, Jones HB, Riccardi D, Price SA (2013). Tissue expression and correlation of a panel of urinary biomarkers following Cisplatin-induced kidney injury. Toxicologic Pathology].

Instead of using whole animals to screen drugs for nephrotoxicity, AstraZeneca could potentially expose cultured renal cells to drug candidates and test for biomarker changes. This would enable them to screen large numbers of potentially therapeutic drugs for nephrotoxic side effects more quickly and in a more cost-effective way. This also complies with the ethical framework of animal experimentation, the 3Rs – reduce, replace, refine – and is what I am currently working on back in Cardiff.

What was your experience in industry like?

My placement at AstraZeneca gave me an invaluable insight into how biopharmaceutical companies work. I was able to use really high-tech facilities, ranging from the equipment I used to carry out immunohistochemistry to the computer analysis software I used to quantify the biomarker changes. In addition, I was able to work with people who are specialists in drug safety assessment and got to see first-hand how drugs progress though preclinical development. The people working at AstraZeneca were very goal-orientated.

They have to meet targets and get results quickly in order to progress promising projects and ultimately make money for the company. The atmosphere was very different to working within academia where timelines can be more flexible and projects can go down a number of different avenues.

Has your experience at AstraZeneca changed your future plans or expectations?

My placement at AstraZeneca has definitely made me consider a career in industry. Just like my PhD, I’d quite like to get a job where there is a strong collaboration between an academic group and an industrial partner as I think you then get the best of both worlds!

Devon Shannon, Exeter University & GlaxoSmithKline

What are you studying and what led you to this?

I’m at Exeter University at the moment, studying molecular biology [Bachelor’s degree]. I’ve already done two years and next year will be my final year. I’ve not always been into science. At GCSE level I wanted to go into art and media studies and be an interior designer. It was one of my teachers who said to me, ‘You’re wasting your talents in science if you go and do art and media studies’. So it was a complete change in career trajectory. One of the things that made me think, yes, I do want to do science as a degree was that I was put into a team of three people for the Royal Society of Chemistry’s Schools’ Analyst competition. Quite geeky, but very fun! It involved A-level students from across the UK competing to see who had the best skills in the lab. That was the first time I’d had any experience in a university laboratory and got my hands on equipment that we weren’t allowed to touch in sixth form!

How did you come to do a placement at GlaxoSmithKline (GSK)?

The course that I applied for at Exeter, molecular biology, was offered as either a three-year course or a four-year sandwich course. My tutors at A-level all said ‘Do the four year course. We know it’s an extra year and that might seem like a lot of effort, but it will be well worth it and’ – the classic phrase – ‘it will look good on your CV’.

We didn’t get a lot of guidance on finding a placement from uni’, it was more a case of independent research to find the job advertisements. I knew it would be a challenge and incredibly competitive, but I wanted to go for a ‘big pharma’ company, because I thought I was more likely to get a diverse range of experiences there than if I went to a small or more specialist company. It was a case of spending ages trawling through websites looking at different company sites and the advertisements they had on their careers pages. I think it was something like 100 applications for every one position. So it was incredibly competitive. One thing that I think really helped me was that the careers advisers at Exeter are absolutely fantastic! There’s a whole building dedicated to careers and they help you with CVs, applications, what to do in interviews and assessment centres and they give you loads of advice. You can show them your CV and have a mock interview to prepare for the real thing. So I managed to prepare quite well and I felt almost like I’d done it before, so that when I was sitting there in the interview – and I sat in three for placements at GSK – I felt quite comfortable, like I knew what I had to do. One interview was with their respiratory department, one was with immuno-inflammation, and one with their pre-clinical imaging team, which is where I actually got the job.

What are you doing there?

My job title is In Vivo Imaging Scientist. What we’re aiming to do is to use MRI and μCT to look at diseases and how they progress in live animals. Basically I’ve been working out how to study fibrosis. Fibrosis is a progressive disease that takes years and years to develop, so, as you can imagine, if you’re trying to study it in humans then you’re going to be there a long time waiting for the chronic stages. Similarly in animals, once you’ve induced the disease, it takes a long time to develop, so you have to wait quite a while before you can measure it and work out if any drugs you’ve used have actually worked. So what I’m looking at doing is developing a new mouse model which should hopefully give you a read-out of where the fibrosis is developing within a few days to a few weeks. That will significantly shorten animal studies and then you’d be able to say yes or no, this drug looks like it is or isn’t working much earlier on. This is great for lead optimisation, so you can progress effective drugs to clinical trial much quicker.

One of the reasons why I applied for this job is because in vivo is something we don’t get the opportunity to do at uni’.

What was your experience in industry like?

Going into an industrial lab is a completely different world from university. There are things at university that you think of as being very advanced because you’ve never used them before, such as Gilson pipettes and centrifuges, until you go into GSK and suddenly you’re confronted with equipment you’ve never seen before! What you learn in university is transferable and you’ll be able to use the basic lab skills you’ve learnt, but there is much more high-tech equipment in the lab, combined with more complex processes. It really is a steep learning curve.

The atmosphere in the lab is very much the same as in the university lab, where you’re all chatting about work but it’s a mutual interest, so sometimes it doesn’t feel like you’re working. It is a very friendly atmosphere.

Has your experience at GlaxoSmithKline changed your future plans or expectations?

It’s not changed my plans, but it has confirmed that this is what I want to do. I think it’s probably increased my confidence that I can do this. Now, instead of thinking ‘Oh, God, that’s going to be loads of education and loads of exams to get there’, I’m thinking, actually, I’d really, really like to work towards that.

All animal studies were ethically reviewed and carried out in accordance with Animals (Scientific Procedures) Act 1986 and the GSK Policy on the Care, Welfare and Treatment of Animals.