Genome editing as a scientific and clinical tool applied to preimplantation embryos (Professor Dagan Wells)
PROJECT TITLE
Genome editing as a scientific and clinical tool applied to preimplantation embryos
SUPERVISORS
Dr Nada Kubikova
DESCRIPTION OF PROJECT
It has been proposed that genome editing methods, such as CRISPR-Cas9, could be utilised during the first few days of life (the preimplantation stage of development), potentially allowing the correction of mutations responsible for serious inherited disorders in affected embryos. Such an approach is attractive from a technical perspective, as the preimplantation embryo is the only developmental stage where every cell of the individual is readily accessible, making it easier to introduce the reagents required for genome editing. However, the possibility of applying CRISPR and other genome editing methods to human embryos remains controversial due to significant safety and ethical concerns. Additionally, our previous research suggests that human embryos struggle to process breaks in the DNA which are produced when CRISPR-Cas9 is used, sometimes leading to breakage of chromosomes and other genetic abnormalities. We hypothesise that this is a consequence of a DNA repair deficiency that exists during the first few mitotic divisions after fertilisation.
This project will seek to identify the genome editing methods most suitable for use in human embryos, whether attempting to ‘repair’ a mutation for clinical reasons, or to deliberately disrupt a gene for the purposes of scientific research. Different strategies for delivering genome editing reagents will be explored. Additionally, attempts will be made to characterise DNA repair capacity during early development, revealing developmental phases where the use of genome editing may be especially hazardous, and identifying the specific types of repair pathway used.
Training Opportunities
The successful applicant will receive training in a wide range of cutting-edge molecular methods, including next generation sequencing, long-read sequencing, immunofluorescence, transfection using nanoparticles, bioinformatics, and genome editing techniques such as CRISPR.
FUNDING INFORMATION
This is a funded DPhil (PhD) covering tuition and college fees and with an allowance for living expenses, supported by the O’Sullivan Family Charitable Trust.
HOW TO APPLY
To apply for this research degree, please click here.