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Alteration of gene expression is fundamental to many diseases. A better understanding of how epigenetic proteins affect diseases provides a starting point for therapy development and the discovery of new drug. We hope that this area of rersearch will ultimately provide leads to finding new treatments for dementia.

Q: What is the link between genes, chemistry and new drugs?

PB: Chemistry sits between a gene and a drug, and what sits in there as well is the field I work in which is epigenetics. Genes control our body but every cell in the body has the same genes and we have very different cells: red blood cells, neurones, bone cells. Those genes are exquisitely controlled by a system called epigenetics. Drug discovery sits between the genes and the medicine and tries to manipulate those genes to actually treat a disease. In epigenetics, which is a new area I work in, we try to link up with drug discovery and use drugs to control genes to treat disease.

Q: How do you go about finding new drugs?

PB: It is a complicated process, of course. We have to first identify a target, which is a protein or something in a cell that we think is doing the wrong thing, and we want to identify that which is the most challenging part. From there we try to develop a way of testing something against that protein or that target and we also try to find new molecules that will interfere with that, hopefully in a positive way, to have a therapeutic effect.

Q: What drug targets has your work focused on?

PB: We are currently working on epigenetic targets. We think that epigenetics are key to controlling how genes are expressed. We try to find molecules that will affect epigenetic proteins, to try and affect those genes as drugs.

Q: What are the most important lines of research that have emerged in this field over the past 5 to 10 years?

PB: The whole field of epigenetics drug discovery is fairly new, it's only been in the past 5-10 years that people have actually looked at it. The concept that drugs can work by turning genes on and off is a new idea. We are seeing effects initially in cancer but we hope to see epigenetic drug discovery be used in many other areas. The concept that epigenetics applies to many different diseases is a pretty new idea.

Q: Why is your line of research important, why should we fund it?

PB: What we will be doing now is looking at treatments for dementia. Dementia is a horrible disease that affects almost 1 in 10 people in the UK over the age of 65; Alzheimer's disease is the most common form of dementia. As people live longer, they don't die as frequently from heart disease or cancer, the number of people getting dementia is increasing dramatically; that is horrible for them, for their families and also for all of us as tax payers who have to pay the NHS to take care of these people. Although that may sound very negative, there is a lot of research going on in dementia and we would like to help in that process to find drugs for dementia. Due to our existing interest in epigenetics, we want to find new drugs that utilise epigenetic pathways and modulate those genes that we think will be useful in dementia.

Q: How does your research fit into translational medicine within the department?

PB: In the Nuffield Department of Medicine we span a whole range of research, from a very early understanding of biology and how cells and biological systems work, all the way to testing things in a clinical trial to see if they are actually useful as drugs. Medicinal chemistry sits in the middle of that. We don't really do the basic science, we take the basic science and understanding of how disease and biology work, pick out those key targets that we think are useful to interfere with, and try to develop treatments for them. If we find something useful then eventually that will be tested at the far end of the transitional pipeline in the clinic.

Paul Brennan

Medicinal Chemistry

Professor Paul Brennan research focusses on epigenetics: the mechanisms that control gene expression. He studies how chemical probes interfere with epigenetic enyzmes that can be targeted to treat various diseases. Epigenetics combined with disease biology will ultimately accelerate drug discovery.

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