Words By Rosie Marilyn Burgess
On 1 October, Liberate the Debate had the pleasure of spending an evening with Dr Güneş Taylor on Zoom. Dr Taylor is a postdoctoral research fellow at The Francis Crick Institute in London, working for the Robin Lovell-Badge Group. The Lovell-Badge Group is a stem cell biology and developmental genetics laboratory, whose research focuses on how early cells make decisions about differentiation during embryo development. Their work also focuses on how structures, such as the pituitary gland of the brain, relate to stem cells and their development.
Currently, Dr Güneş Taylor is conducting research into sex determination, a process which is based upon the fact of male mammals having X and Y chromosomes and female mammals having two X chromosomes. This is in the aim of studying the effect of genes on these chromosomes, and subsequently across the whole genome to work out how they work together to form ovaries and testes. Learning about sex determination is important as it aids our understanding of what can happen when a person’s genes do not match their biological sex.
At her talk, Dr Taylor spoke about how she uses chicken embryos to investigate the development of gonads in chickens. Chickens are one of the original developmental models, having been the subject of scientific enquiry as long ago as 1628. Discoveries resulting from such investigations include knowledge about the function of arteries, T and B lymphocytes, and veins to name just a few. The humble chicken was even used by that most influential of Western philosophers, Aristotle, who conducted embryology using chicken embryos. Interestingly, chickens only have one ovary rather than two. Dr Taylor uses CRISPR-CAS 9, which is the system which we use to edit genomes, to edit FOXL2, a gene which codes for a forkhead transcription factor. The protein has a fork-head DNA-binding domain which plays a role in ovarian development and function. Dr Taylor is interested in this because understanding how something develops is important for understanding how things go wrong. FOXL2 also happens to be a marker for ovarian differentiation and is required for granulosa cell differentiation. Furthermore, the FOXL2 protein prevents the formation of testes by suppressing the expression of SOX9. In the adult ovary, FOXL2 regulates granulosa cell differentiation and also supports the growth of preovulatory follicles.
Finally, Dr Taylor spoke about CRISPR-CAS 9 in greater depth. CRISPR is a two-part process used for gene editing. In Dr Güneş Taylor’s project, she uses CRISPR-CAS 9 to edit FOXL2 in order to produce mutant embryos, and therefore to investigate them. CRISPR works by using “spacer” sequences that are then transcribed into short RNA sequences, known as “CRISPR RNAs” or more commonly as “crRNAs”, which are capable of guiding the system to matching sequences of DNA. When a DNA target is found, CAS 9 – one of the enzymes produced in the CRISPR system – binds to the DNA and then cuts it, shutting the gene off. Dr Taylor explained that there are new modifications being released on a yearly basis in which CAS-9 has been modified to make it more accurate. So, what’s the use of all this? Well, CRISPR could be used to edit the human genome to possibly eradicate diseases in the germline, such as muscular atrophy. These are single-gene disorders which are not inheritable. Not only this, but CRISPR could also be used for therapies in somatic cells.
Dr Taylor also discussed the regulations to which these treatments must be subjected. The Gene Therapy Advisory Committee (GTAC) was set up in 1993 to regulate the use of any kind of gene therapy. Every request that is made to carry out such treatments on a human must be approved by their ethics committee before it can go ahead. The regulation prevents any gene therapy from being used to select characteristics for non-medical purposes. If a germline gene therapy such as CRISPR-CAS 9 has the potential to eradicate a disease, perhaps reproductive diseases, then the long-term costs of treating lifelong diseases could be drastically lowered.
At the post-talk discussion, important questions were raised. One such question concerned the effectiveness of such treatments; would it ever be effective enough to not need constant post-fertilisation screening of implanted embryos? Will the risk of germline therapy ever be minimal enough pre-implantation? What about areas of the world without universal healthcare, will it be only the elite that will be able to access this therapy?
And on a large scale, could germline therapy result in a society that is less accepting of people who are different or have a disability?
Hearing Dr Güneş Taylor talk proved to be very exciting, it raised new and important ideas about the future of CRISPR and genome editing. I, and I’m sure many others, are looking forward to seeing what research her lab produces next.