A Do-It-Yourself Approach to Drug Discovery


I have always been interested in science and biology, in solving problems and discovering new facts. However, I realised early on in my academic career that in order to be fulfilled, I had to take my research to the point where I could achieve that old cliché of "making a real difference." For me, academic research was just too far removed from the clinical applications of science. There is little doubt that no disease would be cured without the collective efforts of academic scientists, yet I could not imagine how my own day-to-day forays into insulin signalling would really affect diabetic patients.

On the M40 leading into London, a prominent display of graffiti asks "Why do I do this every day?" I made the conscious decision to work in an environment where I rarely needed to ask myself that question. I now work for a small drug-discovery company called ProXara Biotechnology, which I was involved in founding. We hope that the technology we develop there will allow new drugs to oneday reach the clinic. My path to this position has involved not only hard work but also a lot of luck.

A Mentor's Influence

As many people will find, at some point in your life you will come across a person who has a deep influence on you--a mentor. I was lucky enough to find one early on. After receiving my bachelor's degree in biochemistry at the University of Bristol, I arranged to spend a year working as a research assistant at the University of Pennsylvania in Philadelphia. My supervisor there, Daniel Malamud, was the sort of boss everyone would love to have. He was successful and ambitious, he loved his job, and he always had time for the people around him. He was excited by new ideas, no matter how wacky, and I came to realise that these were all the traits of a great entrepreneur. He managed the remarkable feat of running not only a successful academic research group but also a biotechnology company. In fact, it was there that my career ambitions first turned to biotech.

After my year in Philadelphia, I returned to the University of Bristol to study for a Ph.D. in the lab of Jeremy Tavaré. My research topic was the mechanism by which insulin stimulates the translocation, or movement, of the glucose transporter GLUT4 from inside fat cells to their surface, where it facilitates the uptake of glucose into the cells. This is a process that is defective in patients with type II diabetes, whose cells become very resistant to the actions of insulin.

Although I found these years of academic research stimulating, the academic career track, with its grant applications and teaching responsibilities, was not appealing. I took an evening class in Business and Finance at the City of Bristol College with the aim of broadening my career options, and as my Ph.D. progressed I began seriously weighing them up: academia versus industry, biotech versus pharma, and even nonlab jobs such as science administration or editorial positions. However, my mind constantly came back to biotech and the idea of working in a small company whose aims you believe in and in which you play a critical role.

Much of my Ph.D. research involved monitoring the movements of GLUT4 within live cells using time-lapse microscopy. By tagging GLUT4 with a green fluorescent protein, we could visualise its translocation to the plasma membrane of cells in response to insulin. Presentation of this sort of data at meetings drew the attention of some industry representatives, who would occasionally approach Jeremy with a view to developing such technology for use as a drug screen. In this case, that screen would allow the discovery of molecules that could mimic the effect of insulin in causing GLUT4 translocation.

At one such meeting, Jeremy and I eventually started mulling over this idea. Perhaps it was the meeting's idyllic location in the Rocky Mountains that made it seem like a good idea, but we decided that, yes, it would be possible to develop such a drug screen, and why not develop it ourselves? Not only that, but we were aware that the functions of other important proteins involved in diseases such as cancer and inflammation are also regulated by their location in the cell. We realised that discovering molecules that modulate the location of these proteins would provide a novel way to treat such diseases.

A Steep Curve With Varied Tasks

We spent the next 18 months working very hard, on a very steep learning curve, to obtain start-up funding for a company based on these ideas. During this time our current CEO, Paul England, also became involved in the enterprise, and his vast experience in academia and industry have been invaluable. ProXara was finally incorporated as a company in March 2001 with funding from Sulis (a fund held by the universities of Bristol, Bath, and Southampton) and Catalyst BioMedica (an investment arm of The Wellcome Trust). We were able to employ another four scientific staff members and begin developing our technology in earnest.

It has been incredibly exciting to see our idea grow into a small company, and I feel that I have learnt so much more than I would have in a large company; with such a small team it is essential to be a jack-of-all-trades. Day-to-day life involves not only labwork but many other aspects of running the company, from patent searching and writing to financial budgeting, computing, and writing reports and presentations. And even in the lab, we see the whole drug-discovery process, from designing a screen to developing and optimising it in cells, automating its use with robotics, using it to test compounds for activity, to eventually identify and then validate hits.

Since our first steps we have become a close-knit team, an aspect of small-company life that I find very rewarding and motivating in contrast to the often solitary arena of academic research. Future expansion of the company will inevitably mean more specialised job roles, but the five of us have had an excellent opportunity to decide which aspects of the company we find most exciting.

Funding for small companies tends to be short-term, so choosing to work in this environment involves taking a risk with job security. Funding is also often dependent on the company hitting stringent financial and scientific milestones. So on occasion, the job can be stressful, particularly if a deadline for a scientific goal is looming or if funding is running short. I am very optimistic that ProXara will continue to be successful, but in any case I am confident that the wide range of skills gained while working for a start-up will make any of our scientists highly employable in any other biotech or pharma company.

For more information on ProXara, visit the company's Web site.

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