To be successful in drug discovery, researchers must look beyond their own work to the bigger picture, and identify opportunities to set in motion the steps necessary to translate discoveries into treatments. This process can’t be undertaken alone – it necessarily means involving other key partners, including industry, and problem solving in new ways. It can be a daunting task, but is a fundamental step in making our research have real-world impact, especially when facing a challenge like dementia, for which there are currently no disease-modifying treatments. For Professor Caleb Webber, Group Leader at UK DRI at Cardiff, this comes naturally, and the process of meeting, discussing and discovering with others is one of the most enjoyable and rewarding aspects of the job.
“It's comparable to when you used to go round to a friend’s house and they'll play you some new music you’ve never heard. Finding out about new science is like discovering a new band as a teenager. I love working with people and hearing about new areas of biology.”
Professor Webber is a self-confessed ‘dot-joiner’. Whether he’s seeking out the missing link in a genetic pathway or playing matchmaker at a workshop, he is always looking to build new networks in the pursuit of solving the complex puzzles behind brain disorders. As the informatics theme lead at the UK DRI, Professor Webber convenes experts in discovery research to exploit the full potential of data generated from the institute and reveal novel insights into disease mechanism. This exercise is crucial given the current paucity of successful therapeutic targets in the neurodegeneration field.
In his own research programme, he is aiming to identify common processes and genetic pathways that underpin the diseases that cause dementia. Unusually, his lab is an equal mix of cell biologists and bioinformaticians, demonstrating his success at seamlessly dovetailing these two disciplines. The team start by probing a set of candidate genes that may be impacting disease, finding out which cells they are expressed (present) in, what their function might be and what else they interact with to build potential disease networks. He believes that by studying gene expression through analysis of the transcriptome, scientists can begin to understand what the cell is ‘thinking’ in the earliest stages of disease.
“If you look back at medicine in the past, the patient went to a doctor who would examine them and tell them what was wrong. Modern medicine takes a different approach by asking the patient about their experience. In a similar way, I like to ask the cell what it thinks is going wrong, and we do that through systematic measurement of gene expression.”
To bridge the gap between discovery research and the clinic, Professor Webber has designed a series of elegant experiments using induced pluripotent stem cells. First, he measures the gene expression of cells exhibiting disease. Next, the team look at the gene expression profiles from healthy cells that receive a drug dose. By comparing these profiles following disease and drug administration, he is able to match treatments that oppose the effects of the disease.