Genomics of inflammation and immunity
The immune system must maintain a delicate balance; it should be sensitive enough to eliminate invading pathogens while being tolerant of the body’s own cells. Immune-mediated diseases can occur when the immune system gets this balance wrong and attacks cells and substances typically found in the body. These diseases are known to “run in families”, suggesting that inherited genetic risk factors play a role in susceptibility. The aim of our research is to improve our understanding of immune-mediated diseases by identifying and functionally characterising the specific regions of the genome that influence disease risk, progression and response to therapy. We undertake both computational and wet lab research in order to achieve these goals.
The Anderson Lab currently consists of 18 people from a diverse range of backgrounds, including genetics, mathematics, medicine, computer science, cell biology and immunology. To date, our research has focussed on the inflammatory bowel diseases (Crohn’s disease and ulcerative colitis), primary biliary cirrhosis and primary sclerosing cholangitis. Over 280 regions of the genome have been associated with at least one of these four diseases, and our group has played a key role in this success. We are currently undertaking whole-exome and whole-genome sequencing-based association studies across tens of thousands of IBD patients from the UKIBDGC and IBD BioResource to identify rare variants associated with IBD. We are collaborating closely with Mark Daly’s group at the Broad Institute, who are generating a similar dataset, to complete the genetic susceptibility map for IBD. By combining our genetics data with the rich phenotypic data that exists across the more than 30K UK IBD samples, including structured data ascertained from electronic health records, we are now identifying loci underpinning variation in disease course and drug response.
The majority of association signals identified via GWAS are driven by non-coding variants that influence disease risk by perturbing gene expression. However, our knowledge of the regulatory genome lags significantly behind that of the coding genome, making it difficult to know which genes are ultimately dysregulated to bring about disease. To tackle this problem for IBD, we are sequencing RNA ascertained from single-cells in the gut and blood from hundreds of IBD patients and controls. We are combining these data with DNA sequencing data to identify genetic variants that regulate gene expression in the many cell types within these disease-relevant tissues. We are working together with the pharmaceutical partners of Open Targets and Crohn’s Colitis Foundation to turn these data, and that from the rest of the research community, into candidate drug targets for IBD.
In our wet lab, we are currently undertaking genome-wide CRISPR screens using primary and iPSC-derived immune cells to identify the cellular mechanisms perturbed in IBD and better understand the biological basis of variation in drug response. We also undertake some functional follow-up work to understand the cellular mechanisms perturbed by variants identified in the studies outlined above.
We have a wide range of very exciting projects underway in our multidisciplinary team, and if you’d like to know more about these please visit www.andersonlab.info. We’re always on the lookout for motivated people to join the group, including those with personal fellowships who think a period of time working in the team will benefit their research. So, if you’re interested in our work, please send one of us an email and include your CV.
Dr Carl Anderson
Group Leader and Director of Graduate Studies
Carl is a statistical geneticist interested in using genetic and genomic data to further our understanding of common complex diseases. He heads the Genomics of Inflammation and Immunity group at the Sanger Institute. He is also the Institute's Director of Graduate Studies.
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The Human Genetics Programme is driving a step-change in our understanding of genetic causes and biological mechanisms of disease susceptibility ...
Our research is highly collaborative and we are fortunate to work with many great scientists and clinicians from all around the world.
The UKIBD Genetics Consortium (UKIBDGC) comprises clinicians and scientists from throughout the UK. The aim of the group is to identify and understand the regions of the genome that determine disease susceptibility, course and response to treatment.
The International IBD Genetics Consortium has brought together clinicians and scientists from around the world to put together a cohort of over 20,000 IBD patients and 40,000 controls. The UK IBD Genetics Consortium plays a central role in the IIBDGC.
UK-PBC is a unique collaboration between patient groups, doctors, scientists and industry with a shared interest in increasing understanding about, and treatment for the autoimmune liver disease Primary Biliary Cirrhosis (PBC).
The aim of the IPSCSG is to coordinate PSC research projects between leading acadmic institutions worldwide. Both basic and clinical research groups are represented, enabling translational research that would otherwise not be feasible.
Dr Tim Raine is a practising clinician with an interest in inflammatory bowel diseases (IBD) and mucosal immunology. His research is focussed on understanding the regulation of the gastrointestinal immune system
Open Targets is an innovative, large-scale, public-private partnership that uses human genetics and genomics data for systematic drug target identification and prioritisation.
The Crohn's and Colitis Foundation is a volunteer-driven non-profit organization dedicated to finding cures for Crohn's disease and ulcerative colitis and improving the quality of life of children and adults affected by these digestive diseases.Carl is a member of the Foundation's Genetics Initiative, along with Ramnik Xavier (Broad Institute) and Thad Stappenbeck (Wash U), and they part-fund our single-cell gut eQTL work.