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Career so far

Following a degree at Cambridge University I worked, and studied for a PhD, with Sohaila Rastan and Neil Brockdorff at the MRC Clinical Research Centre, moving to the MRC Clinical Sciences Centre following its opening. This provided me with a training in both classical and molecular mouse genetics. During this time I demonstrated that methylation of CpG islands was a general feature of the inactive X chromosome. As part of the group I helped to clone and characterise the Xist locus at the X inactivation centre. I subsequently showed that genomic imprinting of Xist is mediated through DNA methylation.

I moved to the Dept of Molecular and Cellular Biology in Harvard for my post-doc as a Jane Cofin Child’s fellow. I worked with Liz Robertson, gaining experience in developmental biology, stem cell biology and gene targeting. Using transgenics I defined the enhancers controlling expression of the Nodal gene, and (in collaboration with other post-docs) systematically deleted these enhancers in order to define their function. During this time I developed an interest in left-right patterning: Nodal is expressed on the left but not the right hand side of the embryo.

I returned to the UK with an MRC Career Development Award (and then an MRC Senior Fellowship), allowing me to establish my own group at MRC Harwell. Here I combined my training in mouse genetics with my interests in left-right patterning, establishing the first genome-wide ENU-driven recessive genetic screen at Harwell. This identified primarily genes that are involved in cilia – either for cilia structure, cilia motility or genes encoding proteins that localise to cilia. This led me to become a cilia biologist. I have helped to organise the European Cilia Meetings since they started in 2012 and I run the basic science workgroup for BEAT-PCD (https://beat-pcd.squarespace.com), an EU funded COST action aimed at bringing scientists and clinicians together to promote and develop therapies for PCD.

Can you explain what you do at MRC Harwell Institute? 

No two days are the same. Nowadays I rarely get to work at the bench. Instead I meet with colleagues in the lab to discuss science, I read scientific papers, and I write about the science that we do. I also travel to attend conferences and to visit scientists in other institutions – this usually involves presenting our work.

What led you to choose a career in this field?

I’ve known I wanted to be a scientist for as long as I can remember, but genetics became my key interest from about 15. At the end of my PhD I saw an early stage mouse embryo down the microscope – if I close my eyes I can still see the beauty and simplicity of its structure to this day. Questions about how genetics controls the establishment of this pattern have fascinated me ever since. My interest in cilia (which we now know are required to pattern the embryo) developed over the past decade and I now find myself thinking about what happens in the cell as often as I think about the organism or the tissue. 

What drives you? Has this changed over the years? 

It is hard to describe the feeling of finding something out for the first time. This is rarely the eureka moment that we see in movies, instead the knowledge slowly builds until you finally realise what you have found. As I have progressed, the team of people I work with have become ever more important and these interactions make me want to come to work every day. One of the greatest pleasures for me these days is seeing my post-docs and student achieve.

What has been your biggest breakthrough in research in the last 10 years? 

Identifying and then placing Pkd1l1 in a genetic cascade that combines genes with a physical flow of liquid: this genetic cascade controls left-right patterning of the embryo. 

What is your ultimate goal as a researcher? 

To understand. To be able to answer the questions “why?” and “how?”

Tell us something interesting about yourself

My PhD supervisor was a student of Mary Lyon’s at Harwell.
 

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