 The brain and the immune system are isolated from each other in your body. When that immune brain divide breaks down it can contribute to disorders of the brain including multiple sclerosis. That can be a real problem you want to keep these two separated. What we've discovered is that in fact key elements of the immune system have important jobs in the brain, different kinds of jobs and we only discover that by wondering what they were doing in the brain in the first place. During early brain development you actually make far too many connections called synapses. You need to eliminate very many of them to sculpt mature brain circuitry. Failure of that kind of pruning process can contribute to disorders including autism and schizophrenia. We were interested in understanding what actually drives that pruning process and a pioneering study performed in another lab looked at the genes that are involved, looking at genes that are highly active during the pruning process and identified one candidate, an immune system gene and the problem was those genes weren't supposed to be made in the brain at all. We figured this was actually a mistake in the screen but just to be sure we looked to see if we could label those genes in the brain. These genes are called MHC or MHC class 1 and they're famous for their job in the immune system. They are essential for your ability to fight off infections and cancers. We did figure it was a mistake but we looked to see if we could label these immune gene products in the brain and in the next slide you're going to see what we saw which is that in fact the brain is lit up with these immune genes. They're highly expressed, especially excitingly in parts of the brain that are undergoing pruning during early development. So it made us wonder are immune genes somehow involved in this brain pruning process during development? So to test that out we obtained mice that have been genetically engineered to be deficient for these immune system genes and people had looked at them, immunologists had studied them for decades and their brains were overall generally normal. They behaved normal normally but we had a very specific question. We thought maybe if MHC is involved in pruning those immune gene deficient mice would have problems with their pruning process and that's exactly what we saw. Throughout the brain actually throughout the nervous system when you eliminate this specific family of immune system genes you fail to prune developing brain circuits. There are a number of reasons why this is interesting. It means that these immune genes actually have two different roles, one in the immune system and one in the nervous system. We know for example that there are a number of disorders of the nervous system that are influenced by immune challenges so infections and other changes in immune function can influence your vulnerability to things like epilepsy and depression. Those immune brain links have remained very mysterious on a mechanistic level and what our results suggest is that these family of immune genes may actually provide a surprisingly direct link between the immune system and the brain. So for example in early development say during pregnancy or early childhood infections might change the levels of these immune genes at a time when they're busy building the developing brain and in that way immune challenges and infections could directly lead to things like microcephaly or other disorders of pruning like autism or schizophrenia. So that's just in development. In adults we also see that MHC levels rise when the brain is damaged. This is an example of a mouse brain after stroke and we know that after brain injury spinal cord injury or stroke MHC levels rise. Remember I told you during development what MHC does is get rid of extra synapses. In adults there aren't extras. What we see is that at the MHC deficient mice they actually seem to retain their circuitry better so they may not be over pruning in a pathological way. With age MHC levels also rise in your neurons and that again could give rise to pruning that you don't want. We lose connections in our brains as we age and that gives rise to problems with motor function also problems with cognitive function and MHC deficient mice again retain their motor function youthful motor function and don't show the age related cognitive impairments. By this point you might be ready to get rid of your MHC not so fast. Remember it's absolutely essential to your ability to fight off infections and cancers blocking it completely would leave you very vulnerable to those kinds of risks. So what we need is a way to specifically manipulate the MHC function in the brain while leaving the immune function intact. That's exactly what our lab is trying to do. So we've developed a small molecule that we believe targets only the neuronal functions of these proteins and we're now in preclinical testing to see if those peptides will be effective for treating a variety of disorders including epilepsy and stroke. Your body is built from a very small number of molecular machines and they get repurposed for different functions like you could repurpose a shovel as a coat rack if you really needed to. So these immune genes have an important role in the immune system. They've also been repurposed to have an important role in your nervous system. So one of the exciting implications of this I think going forward is that it means that we have drugs that have already been developed and tested for manipulating immune function and it's possible that those already developed, already tested drugs are promising candidates for targeting disorders of pruning in the developing an adult nervous system. Thank you.