Human Genome, Data Sharing and Drug Discovery: A Career Profile with Ian Dunham

Ian Dunham introduces us to his career so far, including working on the Human Genome Project, seeing his work on the cover of Nature and his current role as Director of Open Targets.

Ian Dunham in his office at the Wellcome Sanger Institute, circa 1999. Credit unknown.

Selecting the best drug target is a critical decision in the drug discovery process. Open Targets is an innovative public-private partnership that aims to improve the success rate of new drugs by using open access human genetic and genomic data to identify and prioritize potential drug targets.

Ian Dunham explains how his early interest in biochemistry led him to EMBL-EBI, and his current role as Director of Open Targets.

When did you first become interested in genetics and genomics?

I went to college before something like genomics existed, so I studied biochemistry because I was interested in molecular biology and how organic chemistry is used in living systems. I was fascinated by recombinant DNA and cloning, as well as the ability to take viruses and bacteria and manipulate pieces of the genetic code to create new things.

How did you get involved in the sequencing of the human genome?

One person descends from the floor on a chair, another person sitting on a second chair looks at the other.
Sir John Sulston (left) and Ian Dunham (right) in Sanger’s annual Christmas pantomime.

It was a topic of discussion at the time, and when I started my postdoc with Maynard Olson at Washington University in St. Louis, I suggested that we could clone an entire chromosome using chromosomes. artificial yeast (YAC). Maynard thought I was crazy.

In fact, three years later, I started working on the Human Genome Project, cloning human chromosome 22 with YACs. We published our map of human chromosome 22 in 1995, and that was really the start of large-scale cloning for genome sequencing.

Soon after, I joined John Sulston in training the Sanger Center, now the Wellcome Sanger Institute, located on the same campus as EMBL-EBI. By this point, several groups had started working on the sequencing of chromosome 22, but rather than competing on these different pieces, we decided to work together to put the whole sequence of the chromosome together. We released the footage just before the millennium; it was the first complete human chromosome and a major success.

Where did you go from there?

Cover of the December 1999 issue of the journal Nature, in which the sequence of human chromosome 22 was published. Credit Springer Nature.

Our work on chromosome 22 has become a template for the rest of public sequencing of the human genome, but we have also used it as a template system for further analysis. Basically, we said, we’ve got the sequence, so what now?

We have done several things. One was to try to create the most detailed map of gene annotation. The other was to think about how we might relate the sequence to human variation, which led us to create a chromosome 22 linkage imbalance map, the first of its kind. We could then begin to convert our knowledge of the sequence of the genome into an understanding of how the genome works as a unit. In collaboration with the ENCODE consortium, we have started to map how histone modifications that mark enhancers and promoters change in different cell types.

At that time, the Sanger Institute changed the focus of their research and I was fired. I have always been interested in computing and software, so I decided to convert to bioinformatics, by joining the Ensembl team at EMBL-EBI. Luckily, I then joined Ewan Birney’s group and ended up working on the new version of the ENCODE project.

How was the Open Targets project born?

Male person standing behind table, looking at camera, holding knife for cutting cake.
Ian Dunham celebrating 5 years of Open Targets in June 2019.

Our work was slowly expanding our understanding of genetic and epigenetic signals, leading us to the next hurdle: How do you convert the information generated in the genome project and genetic studies into information useful for drug discovery?

In discussions between Janet Thornton of EMBL-EBI, Mike Stratton of Wellcome Sanger Institute, and Patrick Vallance during GSK days, we discussed what a collaboration between our institutions could look like, forming what is now Open Targets.

The challenge of open targets is to bridge the gap between drug discoverers, who tend to focus on a very specific mechanism, and the broader systematic genomics and genetics, which is useful for understanding which targets are likely to be. be relevant to the disease. I was appointed Scientific Director, responsible for shaping the research program.

Now, as a director, how do you see Open Targets going in the future?

On the public side, I think we’ve had a real impact with Open Targets Platform and Open Targets Genetics, and we want to make sure that these continue to be sustained.

Within the consortium, the guiding question behind our work is: how can we use the existing research agenda and convert it into results that can feed into the drug discovery process? Our experimental research program aims to provide cutting-edge experiments and produce information on disease targets, while our bioinformatics teams work to make sense of the data we generate.

Ultimately our goal is to create a comprehensive data set identifying the targets most likely to be of interest to the disease, but the question is so open-ended that we will not be able to address all aspects of it; we do our best to resolve individual issues, keeping in mind how all the pieces fit together.

Read the full interview on the Open Targets blog

/ Public distribution. This material is from the original organization / authors and may be ad hoc in nature, edited for clarity, style and length. The views and opinions expressed are those of the author (s). See it in full here.

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