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MABRA stands for Multi-scale Analysis of B cell Responses in Ageing
(for the technical summary see here)
Older people do not make immune response to infection and vaccination as well as younger people.  So they are more likely to get infections, and will be more poorly as a result of the infections that they get, than a younger person would.  In addition, sometimes there will be immune dysregulation such that the older person will have a greater chance of autoimmune or inflammatory disease.

Our lab investigates B cells, the cells that produce antibodies and can also help other types of immune cells react to challenge.  So that the immune system can react to almost any challenge the B cell receptor/antibody is pretty unique for each B cell.  So we have about a billion different types of B cell.  We specialise in studying this repertoire of antibody genes in order to investigate how the immune system responds to infection while maintaining tolerance against self.

In this study we are investigating the response to a vaccine against something that we would not normally be exposed to - yellow fever.  The reason we have chosen this is because the immune response is different whether we have seen the challenge for the first time, or whether the immune system already saw it.  In the latter case we will have memory cells that respond to the challenge.  In the UK we have nearly all been exposed to a challenge such as influenza at some time in our lives.  Just because we haven’t “had the flu” doesn’t always mean our immune systems haven’t seen it - if we have a really good immune response we might kill off the flu before we get chance to feel sick! 

So we will be collecting blood samples before and after the vaccine so that we can sequences hundreds of thousands of antibody genes in order to look at the repertoire response to a primary immune challenge.  We will be comparing the response in different people of different ages to try and identify what the main differences are with age.  The large quantities of data that we produce are analysed with the help of computational biologists Professors Franca Fraternali and David Kipling.  Concurrently with this we are making mathematical models of aspects of the immune system which will make assumptions and predictions about quantitative aspects of the immune response such as the degree of antibody gene diversity, and the extent of expansion of different B cells (with Professor Ton Coolen).  Predictions arising from the mathematical models can be tested in the data. 

We hope that a better understanding of how the immune system changes with age will lead to us being able to pinpoint areas for intervention to improve the immune system.  This is especially important since the more we can rely on our immune system to protect us then the less reliant we will be on antibiotics in a world of ever-increasing antibiotic resistance.

We also hope that working across disciplines in this way, and including our whole teams in regular meetings, will help to train a number of post-docs and students in interdisciplinary working. 

Dunn-Walters’ Lab
Faculty of Health and Medical Sciences, Duke of Kent Building, University of Surrey,
Guildford, GU2 7XH
d.dunn-walters[at sign]surrey.ac.uk
@beecellnumbers

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