In a series of interviews we’re hearing from members of the DMDD programme. Who are they? What inspires them? And what do they hope that DMDD will achieve? This month we hear from David Adams, who oversees the production of embryonic lethal knockout mouse strains for the project.
What has been your main area of research in your career so far?
I lead the Mouse Programme (MGP) at the Wellcome Trust Sanger Institute, which generates around 200 genetically modified mouse strains each year. The MGP explores the role of genes in a range of biological processes including in development, immunology and infection, and in metabolism and cancer. I am primarily a cancer geneticist interested in how the immune system controls tumour growth and the genetic wiring of cancer cells. Remarkably this had led me to explore aspects of developmental biology as we try and understand what these genes do.
What inspired you to devote your career to developing animal models of human disease
In all areas of medicine and biology, animal models have contributed significantly to our understanding of disease processes. For example, our understanding of the fundamentals of how the immune system recognises pathogens and cancer result from experiments in mice. The development of induced pluripotent stem cells, which appear to have huge potential in regenerative medicine, was also pioneered in mice. If that’s not enough, the role of literally thousands of mammalian genes in development has been elucidated in mouse model systems. The contribution has been huge. Further, virtually every drug approved for treating patients was tested in rodent models.
What do you think is the most exciting recent development in your field?
This has to be CRISPR. The ability to rapidly alter the genome with unprecedented precision makes generating new animal models significantly easier. In particular, we are able to introduce point mutations found in patients to essentially humanise the mouse genome.
What is the biggest outstanding problem in your field that you wish could be solved?
There are still many many genes where we don’t have even the most basic understanding of their role in development or disease. Cell culture systems will undoubtedly contribute to further understanding, as will the analysis of human tissues, but to really understand what a gene does you need to manipulate it in the context of the whole organism and see what happens. We call this the post-genomics era but in fact we are still very much living in a time where we don’t know how the genome works and how individual genes function. I think there are many surprises and delights still to be found.
Why did you decide to become involved with the DMDD programme?
My role is to represent the Sanger Institute as a member of the DMDD programme. The DMDD is a group of world-leading investigators using cutting edge technology to explore processes involved in development and embryonic lethality. I find the idea of contributing to such a large-scale co-operative endeavour very compelling. It is also wonderful that the data is released to the research community to facilitate further discovery.
What do you hope the DMDD programme will achieve?
So far there have been some big surprises. In particular, the significance of the placenta in development and the high frequency of cardiac malformations in developmental disorders have been a surprise to me. Large-scale programmes such as the DMDD that make no assumptions about how genes work or what they do have the potential to challenge dogma, and that’s what I think the DMDD is achieving.
If you could have been a fly on the wall during any scientific discovery, which would you choose?
I have a particular interest in how the immune system regulates the growth of cancers. In the last few years there have been substantial advances in understanding how T-cells control tumour growth. I would love to have been involved in, or seen first-hand, the development of T-cell checkpoint therapies because these are truly changing people’s lives and a proportion of patients with advanced disease are being cured.
What are you most proud of achieving outside of science?
I have two delightful children, which is a surprise given my genetic contribution. I am also a keen runner like other members of the DMDD (Tim Mohun and Jim Smith) and routinely run 20 km a week. I am currently training for the Cambridge Half Marathon.
Tell us a surprising fact about yourself
I used to breed, raise, and show chickens as a child. I guess this was probably the basis for my interest in genetics. Like everything I do I was extremely competitive.
David Adams is a Senior Group Leader at the Wellcome Trust Sanger Institute, and a joint grant holder for the DMDD programme.