Continuing our series of articles on Great British bioscience pioneers Professor Wolf Reik FRS FMedSci gives us a glimpse at his career at the forefront of research into epigenetics, the study of changes in organisms caused by modification of gene expression, rather than changes in DNA sequences.
He is a molecular biologist, senior group leader and associate director at the Babraham Institute, honorary Professor of Epigenetics at the University of Cambridge and associate faculty at the Sanger Institute.
How did your bioscience career first begin?
I came to Cambridge in 1985 after an MD in Hamburg in Germany where I did my thesis work with Rudolf Jaenisch and got excited about the possibility of a molecular biology understanding of mammalian development. I joined Azim Surani in Cambridge who had just discovered genomic imprinting, whereby genes from one parent can be switched on or off, and as a molecular biologist set out to discover the mechanism of imprinting. I have ever since been fascinated with epigenetic mechanisms of gene regulation and inheritance, and the implications this has for understanding human development.
What are you working on now?
Right now we are obsessed with understanding the mechanisms and biology of global epigenetic reprogramming that occurs in germ cells and early embryos. Epigenetic information in the majority of our cells is pretty stable (and guides programmes important for organ development and function) but this information is reprogrammed and hence largely wiped out in early embryos – presumably so that stem cells are able to differentiate into all cell types in the body. This erasure of epigenetic information also means that epigenetic inheritance across generations may be somewhat limited in mammals (while it is common in plants). Insights into the mechanisms of epigenetic reprogramming are providing us with new approaches to improve the potential of stem cells for regenerative medicine.
What advances have you seen in your chosen field in the last 20 years?
As a scientist I grew up with (pop music and) the molecular biology revolution, which was wonderful because you could begin to seek molecular explanations for so many long-standing questions in biology and medicine. I became fascinated with epigenetics at an early stage of the field where there were tantalising observations in animals and plants suggesting normal rules of genetics and inheritance did not apply. Epigenetics is now one of the fastest moving fields in modern biology with many exciting applications in medicine, biotechnology, and the pharma industry. Molecular biology laid the foundations for the discovery of epigenetic marks and proteins (such as writers, readers, and erasers of the epigenetic alphabet) and thanks to second (and soon third) generation sequencing technology and bioinformatics we can now decipher whole epigenomes (the epigenetic make-up of the genome) before the morning coffee break. A revolution just happening is to be able to do all this in single cells, in order to understand the remarkable plasticity of epigenetic information in development and human tissues during the lifespan and across generations.
What are the 5 key bioscience milestones that you've been part of?
- 1987 Discovery of DNA methylation as the molecular mechanism of genomic imprinting
- 2000-2002 Discovery of large-scale epigenetic reprogramming in mammalian germ cells and early embryos
- 2002 Discovered that imprinted genes regulate nutrient transfer from the mother to the fetus
- 2010-2012 Discovered some of the principal mechanisms of demethylation of DNA leading to global epigenetic reprogramming. Some sequences resist this erasure providing the potential for transgenerational epigenetic inheritance
- 2013-2014 Discovered links between global epigenetic reprogramming and pluripotency of embryonic stem cells
How has BBSRC supported you throughout your career?
After my postdoc I was fortunate to be given a five-year career development Fellowship by the Lister Institute of Preventive Medicine. I have been Head of Department and then also Associate Director at the Babraham Institute in Cambridge since 1994. Babraham receives core funding from BBSRC, which is really important in order to develop long-term ambitious research programmes in basic bioscience, together with investments in high level science infrastructure such as animal facilities or next generation sequencing so that you are able to compete with the best in the world. With the help of my colleagues Wendy Dean and Fatima Santos this allowed me to make inroads into some fundamental questions in mammalian epigenetics. As a result of this support to us and other epigenetics pioneers (including at John Innes Centre, another BBSRC strategically-funded institute) I think that BBSRC can claim some important stakes in supporting the epigenetics revolution in the UK.