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Scientist Focus: Prof Paul Brennan

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Prof Paul Brennan is Head of Chemistry at the Alzheimer’s Research UK Oxford Drug Discovery Institute.

What does your research focus on?

As a medicinal chemist, my research is focused on finding new drugs for dementia. We design and make drug-like molecules and test them in cells that are engineered to behave like brain cells in people with dementia. If the compounds don’t work perfectly, we try to understand why, then design and make new molecules and test them again. We repeat this process many times to find the ideal molecule. When we ultimately find a molecule that does what we want in cells, we will test it to make sure it’s safe and then test it in patients to see if it works to treat the diseases that cause dementia. The whole process from an idea to a new drug might take up to a decade.

Prof Paul BrennanWhy is this area of research important?

Dementia is one the most devastating conditions with very few good treatments. Our understanding of what causes dementia and how to treat the diseases underlying dementia has historically been poor. Anything I can discover as a scientist to help people with the disease, including members of my own family, would be the highlight of my career.

Why did you choose to be a dementia researcher?

I enrolled in university as a mechanical engineering student, but when I took an organic chemistry class, I was immediately hooked and wanted to design and build molecules instead of machines. After my PhD in organic chemistry, I joined the pharmaceutical industry because I wanted to make molecules that improve the lives of people. At Amgen and Pfizer I worked in drug discovery for cancer, pain, urology and respiratory disease. I returned to academia in Oxford because I thought my skills in medicinal chemistry and drug discovery would be well matched with the revolution that is taking place in our understanding of human disease due to genetics and other “omics” technologies. I was very excited by the formation of the Alzheimer’s Research UK Drug Discovery Institute in Oxford and leapt at the chance to work in an area that is so critical to human health.

What do you like to do in your spare time/ outside the lab?

I like to spend time with my family, play pool, read novels and do yo-yo tricks. I spend my weekends fixing up a derelict house I was foolish enough to buy when I moved to Oxford.

What’s the best thing about working as a scientist?

Coming to work and getting to do what I love every day. I’ve had jobs making pizza, flipping burgers, washing dishes and delivering newspapers. I liked delivering newspapers because I got to cycle a lot and the longer you worked, the lighter the load got. As a scientist, I get to face a new challenge every day. Science can be tedious and difficult, but when I discover something new after months or years of hard work and tenacity, it’s one of the best feelings I can have.

What do you think is the most promising area of dementia research at the moment?

Drug discovery is shifting from the idea that a single problem is the root cause of disease towards the concept that complex biological networks gradually become unbalanced until they reach a tipping point, resulting in the diseases like Alzheimer’s. One mechanism for this unbalance may be due to epigenetic changes that build up over many years. Epigenetics is known as the layer above genetics, acting like punctuation in a sentence and thereby controlling how our genes are regulated to deal with our environment. It is beginning to emerge that tweaking epigenetics may be a great way to shift the balance in cells from disease back to health. This is true for cancer and may also be true for dementia. I am very interested to see if we can focus epigenetic drug discovery on treating dementia.

What advice would you give new scientists embarking on a career in dementia research?

Like all types of research, dementia research can be difficult at times, with patience and focus required to persevere through the setbacks that science throws out. It is an exciting time to be a dementia researcher as there is a real momentum building, and the opportunity to be part of finding new treatments for this devastating condition.

If you were stuck on a desert island and could only bring three things, what would you bring?

My freehand Canon yo-yo or my off-string Flight yo-yo. Off string yo-yoing is really difficult and I’d like the chance to practice more, although I’d worry about the sand on the desert island getting into the yo-yo bearings. Can I also bring a kindle loaded with thousands of books? The third thing would be a box of wood-working tools so I could build my own boat and sail home.

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