Associate Professor of Human Genetics
Radcliffe Department of Medicine (RDM)
MRC Weatherall Institute of Molecular Medicine (MRC WIMM)
Tell us a bit about your role
I am a Molecular Geneticist with a wide background in developmental biology, genetics and sequencing technologies. My main research interests are driven by some of the most fundamental questions in biology: how can the genetic information encoded within a single cell (the fertilised egg) be accurately copied during development and coherently translated into reproducible patterns to organise coherent multi-cellular organisms? Using a human genetic approach, I aim to understand how and why new mutations are introduced in our genomes. I study this question directly in the tissue where most new point mutations originate – the human testis – by asking how cell fate decisions and stem cell dynamics in this organ influence germline mutation rates and human disease.
I originally qualified with a degree in ‘Agronomy’ (agricultural Engineering) and spent a fair amount of time in potato and medicinal crop fields as an undergraduate. During my PhD, I studied the development of the fruit fly model organism Drosophila nervous system at the ‘Free University of Brussels’ (ULB). I quickly became aware that molecular biology was an essential research tool and as I had no formal background in this field, I trained at Cornell Medical School and Rockefeller University (New York), where I cloned and characterized several Drosophila developmental genes. During this time, I also broadened my interests in developmental biology to higher organisms and decided to move to the UK to switch my attention to the study of nervous system patterning in the chick embryo. It was a logical and attractive next step to progress to studies in humans, and in 2000 I joined the Clinical Genetics Research Group of Professor Andrew Wilkie at the MRC Weatherall Institute of Molecular Medicine (MRC WIMM) in Oxford, as a Senior Postdoctoral Fellow. Today, I am still based at the MRC WIMM where I am currently Associate Professor of Human Genetics and head a research lab focusing on studying new mutations occurring in the male germline.
MRC WIMM, RDM and Medical Sciences are a perfect fit for my wide-ranging scientific interests, covering fields such as genomics, ageing, reproductive biology, evolution, clinical and population genetics, epidemiology, Ethics and developmental biology to name but a few. This has been instrumental to my career and probably explains why I have remained based at the MRC WIMM for the last 2 decades.
What is the most meaningful aspect of your work?
Over the years, I have developed techniques to detect ultra-rare spontaneous mutations in sperm and testes associated with specific human disorders and discovered a process called “selfish spermatogonial selection”. This phenomenon explains why mutations associated with some severe spontaneous disorders arise in our genomes up to 1000-fold more frequently than background and are more common in the children of older fathers (Paternal Age-Effect). Because most new mutations happen in the father during sperm production, studying how sperm is made and how it accumulates DNA mistakes is important to understand genetic diseases. New, so-called, ‘selfish’ mutations hijack the way sperm is produced to their own advantage and become more abundant in sperm as men get older.
This work has important implications for disease and has attracted attention on the impact of paternal age on new mutations – selfish selection is predicted to be particularly relevant to disease risk in ageing reproductive populations. It has also led to new recommendations on the upper age limit for semen donation.
Can you tell us about something you've done, contributed to that you're most proud of?
The work I have done on new mutations has highlighted basic biological differences of new mutation occurrences in males and females.
From a more pragmatic point of view, this work also emphasizes that both parents contribute to the genetic health of their future children, which provides an important paradigm shift of how, as a society, we tend to think about issues of guilt, blame, and responsibilities, where the mother is often seen as the guilty party when things go wrong with fertility issues or genetic disease.
What changes would you most like to see in the Medical Sciences in the next 100 years?
Although it can be reassuring to be among peers who ’think alike’, today, most will agree that diversity and inclusion are important factors for creative and collaborative research. However, we still have a long way to go to erase the remaining prejudices and to accept contributions from individuals of all backgrounds, gender, ethnicity and abilities.
I am a strong believer in women having a vital role to play in the transformation of science, but not just as excellent scientists. This is not just out of an ethical concern for equity, however. I am mindful that we must be careful not to promote women simply to have them access and perform ‘patriarchal’ science, designed by men. Women should help give science a stronger conscience, building a formative ethical dimension and a level of accountability, which among others, must include reflecting on (and hopefully undoing) some of the damage ‘testosterone-driven’ science has done to society over the past centuries.
Hence the challenge will be to embrace differences and to promote inclusive science without rendering it ‘monochromatic’, but rather support a multi-faceted approach that truly respects and promotes different points of view and ways of doing things. Science can have masculine, feminine and/or non-binary undertones but must be designed and thought through carefully by individuals of all and always more diverse backgrounds.
It will be essential to continue to educate the next generations to respect and embrace these differences in order to catalyse transformative changes and make progress. I would hope that it will not take another 100 years, before equity, inclusion and equal opportunities to education for individuals of all backgrounds become a reality, a true fabric of our society, that no longer requires to be written in laws, debated or argued for