Research Interests Translated

I recently updated the information on my website, and in doing so I decided to produce two versions of my research interests. The first is for other scientists, and the second is a translation for lay people. I would be interested to know how people think this is pitched; is the lay-information too confusing, or is it too simple and patronising?

I think every scientist should try and do this at some point. It is an interesting exercise to see how well you can communicate and summarise the entirety of your research in a way that doesn’t use the shared lingo and knowledge base that you have access to when taking to other scientists. Plus, of course, communicating your work to the world outside of academia is generally A Good Thing.

My Research: Scientist Edition

My research interests are focused towards the usage of new sequencing and genotyping technologies in understanding human disease, particularly the contribution of rare variants to complex disease. Powerful technology available both now (high density genotype chips, second-generation sequencing) and in the mid-future (third generation sequencing) allows us to look at classes of variation far outside the standard common SNPs that we have looked at previously.

I look at using large-scale datasets such as produced by the 1000 Genomes Project and HapMap3 to perform imputation on existing reference data; studying how these new datasets can improve our inferences on disease genetics, and how to best design our imputation algorithms to use this new data. I am also interested in new tests for rare variant association to allow us to overcome the power barrier inherent in rare-variant association.

I also have interests more generally in the selective and population genetic influences on the genetic variants that lead to disease in human populations, and discovering what forces shape the allelic spectrum of common complex disease.

I mostly focus on autoimmune diseases, such as Crohn’s Disease, Ulcerative Colitis and Type I Diabetes.

My Research: Lay-Person Edition

My research involves trying to find out how differences in each person’s DNA influences how likely they are to get different diseases, such as inflammatory bowel disease and diabetes. I want to track down which regions of DNA are associated with disease, so that we can explore what is in this region and find out what things are causing the disease (for more information on what this can tell us, see this essay that I wrote on the subject).

In recent years, a number of studies, called Genome-Wide Association Studies (GWAS), have looked at exactly this, and a number of very important genes and DNA regions have been discovered, leading to new ways of understanding and treating these diseases. For instance, GWAS studies have shown that the Autophagy pathway, a mechanism that our body uses to break down parts of our cells that are damaged or not needed, is disrupted in a type of Inflammatory Bowel Disease called Crohn’s disease.

However, while we have found a lot of disease genes, we know that there are a lot more out there. We suspect that this has something to do with the way we have been looking: because the technologies we use have only let us look at variations in the DNA that are relatively common (more than 5% of people have them), we haven’t been able to look at how rare variations influence disease. However, new technologies, such as machines that let us sequence a large amount of DNA, or silicon chips that let us look at a large number of variants in a large number of people, are allowing us to look at these rare variants. As time goes on, the technology will only become more powerful.

I am interested in using these technologies to find regions of the genome that contain rare variants that influence disease; this requires new ways of thinking about how we look for these variants, since the old ways weren’t created with rare variants in mind. One thing I am working on is called Imputation: this involves using new technologies to look at which variants tend to occur together in one sample of people, and using this information to work out what variants are present in other people from the some population: this allows us to go back and get new information on rare variants from old information we collected before, potentially giving us new-techology style information from old-technology data. I also want to try and combine this information in new ways, to get better at tracking down which regions of the genome contribute to disease. I hope that, taken together, these methods will let me find new insight into autoimmune diseases.

I am also interested in generally what sort of forces act on the human genome; these include random changes in the DNA, people migrating, and natural selection. I want to know how the frequency and positioning of disease-influencing variants is influenced by these forces, and whether this can tell us something about the way disease has occured in populations, both recently and in the distant past.