Nuclear Dynamics ExplainedOur genomes influence nearly all aspects of our daily lives, from our health and well-being to our susceptibility to disease. We carry out basic research to create an integrated understanding of control of genome function in relation to health, immunity and ageing.
Our immune system functions throughout our lives to protect us from infection, but becomes noticeably less effective in the elderly. The causes of this decline lie in part in the mechanisms that control our genome.
B cells produce antibodies, which tag molecules of invading infectious agents, such as bacteria and viruses, to mark them for destruction. In order to respond to new infections throughout life, new B cells must be produced in massive numbers, and these cells have to produce millions of different antibodies to ensure that any potential foreign invader is detected.
Unfortunately, ageing results in a decrease in the number of different antibodies that our B cells produce, which leaves the elderly especially susceptible to infection and disease. We have discovered that this age-related decline in antibody repertoire has its origins in our genome.
Antibody-producing genes are incredibly large and can be likened to a warehouse containing a massive inventory of spare parts. Each B cell combines these spare parts in a unique way such that every B cell produces a single unique antibody in the hope that at least one of the millions of antibodies produced will be a match for any potential invader. This strategy is very effective in young individuals. However, B cells from aged individuals do not use the full inventory of spare parts available to them, which results in a significant decrease in the antibody repertoire. This makes it more likely that infectious invaders can escape detection and result in disease.
Our experiments are aimed at understanding the molecular mechanisms that control our genomes with a particular emphasis on recombination of antibody genes. We do this by applying recent advances in next-generation DNA sequencing technologies to systematically make numerous genome-wide measurements in B cells. We use multidisciplinary and systems approaches to assimilate information on the many different genetic, epigenetic, biochemical and structural parameters that affect genome function with a particular emphasis on gene control.
By integrating the massive amounts of data that we collect we will have an unprecedented view of B cell genome control at the critical stage of their life cycle when they make new antibodies. This will allow us to identify critical genes and factors that are responsible for this declining performance.
This knowledge will be important to understand the processes of ageing, and to develop new clinical strategies and therapies to rejuvenate or prevent the decline of the immune system in later life. This will protect the most vulnerable members of our population from unnecessary opportunistic infections and disease.