Our immune system plays a role in eliminating microbes and cancer cells, but also functions as a sentinel, preventing the emergence of defective white blood cells which could attack our own tissues and, therefore, trigger an autoimmune disease. However, every day patients are diagnosed with autoimmune diseases and nobody really understands why immune safeguard mechanisms have failed. We have described a new factor named BAFF/BLyS, which acts on a subset of immune cells and promotes their survival. Overproduction of this factor leads to the inappropriate survival of harmful immune cells and tissue destruction by these cells. Importantly, the serum of patients suffering from autoimmune conditions contains high levels of BAFF. We have collected evidence suggesting that subsets of white blood cells might have an adverse role in the progression of BAFF-led autoimmune disorders and inflammation. In this project, we would like to identify harmful white blood cells, how they abnormally develop and molecules specific for these cells to be used as targets for therapeutic intervention in various autoimmune diseases. The aim of this work is to find ways to refine treatments of autoimmune diseases by targeting pathogenic cells while preserving the healthy side of our immune system.

All the genes in the human genome are now known, but it is not known in detail how they are regulated in normal development and misregulated in diseases. The fact that the number of genes a fruitfly has is quite similar to the number of genes of a human, has given rise to the idea that vast areas in the genome that do not contain genes have this regulatory function. In particular so called non-coding RNAs outside of genes have been implicated in genome regulation and disease. We study a particular non-coding RNA which when it is aberrantly made leads to the Beckwith-Wiedemann syndrome in which babies are born that are very large and can develop cancer. Our studies will help to understand better how the disease is caused, and will therefore help the families with children who have the disease.

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We inherit genes from our fathers and mothers and, for most of our genes, the copies we receive from either parent are equally active. An important exception to this general rule occurs in a process called genomic imprinting, whereby one gene copy is deliberately silenced. These imprinted genes are important in determining how the fetus grows and how infants adapt their physiology to life outside the womb. But the fact that these genes have one copy that is preselected to being silent poses a risk and makes them particularly vulnerable to mutation events, such as occurs in cancer. Imprinted genes behave in this manner because they are marked in different ways in the male and female germ cells. How these genes are so marked is not fully known, and it is important to find out, because if the marking process goes wrong problems in fertility or developmental abnormalities may arise. By analysing a single imprinted gene in some detail, we have discovered an important part of the mechanism in the germ cell marking event. In this research, we wish to understand this mechanism in more detail and we need to show that it may apply generally to imprinted genes. This work will be done in a model system, but it will provide important new insights for human studies.