Join our team!
If you're interested in joining our team please send Rob an email! We are always keen to hear from motivated scientists interested in doing a PhD or a period of postdoctoral research.
DPhil in Clinical Medicine
Applications to study for a DPhil (Oxford University's equivalent of a PhD) on the Nuffield Department of Medicine's DPhil in Clinical Medicine course are now open for students wishing to start their course in October 2024! Projects are normally developed together with prospective applicants, so get in touch with Rob if you're interested and we can discuss possible projects.
Deadline for applications: December 1st 2023
Molecular basis of neurodevelopmental issues in Cornelia de Lange Syndrome
DNA loops allow enhancers to contact and activate their target genes in the 3D space of the nucleus. These loops are formed and stabilised by CTCF (a zinc-finger transcription factor) and cohesin (a ring-shaped multi-protein complex). Mutations in components of the cohesin complex cause a rare genetic disease called Cornelia de Lange Syndrome (CdLS) which affects between 1 in 10,000 and 1 in 50,000 individuals. CdLS patients exhibit varying degrees of intellectual disability, microcephaly and social anxiety. This project aims to understand the molecular mechanisms linking disrupted DNA loop formation with brain development.
Our lab works with mice that carry a conditional knockout Nipbl allele, as heterozygous loss of function mutations in NIPBL are the most common cause of CdLS. These mice also exhibit cerebellar hypoplasia and altered gene expression in the brain. This project would involve identifying the specific neuronal cell types and genes that are disrupted when embryos are deficient for Nipbl. The student would address this question by generating and analysing multiple genomics datasets from Nipbl knockout mouse embryos and their wild-type littermates. These could include single-cell RNA-seq, single-cell ATAC-seq, spatial transcriptomics, CUT&TAG and Genome Architecture Mapping.
The project would not require the student to undertake any animal work themselves. The project will require a mix of both wet-lab and dry lab work but the specific balance between the two can be adjusted in either direction depending on the preferences of the student.
Investigating the role of genetic mosaisicm in congenital disease
Genetic diseases are usually caused by mutations that are either inherited from a parent or occur de novo in the parental germline. In both cases all the cells in the affected child will carry the causative mutation. However, in some cases pathogenic mutations occur after fertilisation - during early development of the embryo - and in this case, only a proportion of an individual’s cells carry the mutation, a phenomenon known as mosaicism. With improved sequencing technologies, it has become apparent that mosaicism is not as rare as previously thought. Moreover, there are conditions which are much more frequently caused by mosaic mutations. For example, up to 20% of cases of Cornelia de Lange Syndrome are caused by mosaic mutations and the pathogenic mutation is almost always missing from blood cells. Similarly, focal cortical dysplasia, a common cause of epilepsy, is commonly associated with mosaic mutations.
In this DPhil project, you will work with the Beagrie lab (based at the Wellcome Centre for Human Genetics) and the Goriely lab (based at the MRC Weatherall Institute for Molecular Medicine) to study how mosaic mutations affect development and cause disease. Specifically, you will use conditional inducible mouse models to study how cells bearing mutations in known disease genes expand and compete with their wild-type counterparts in different tissues.
DPhil in Genomic Medicine and Statistics
Applications to study for a DPhil (Oxford University's equivalent of a PhD) on the Wellcome Centre for Human Genetics DPhil in Genomic Medicine and Statistics are now open for students wishing to start their studies in October 2024. Please apply here - applications are open until December 1st 2023. The first year of the GMS course will involve short rotations in 2-3 different laboratories, so you don't need to identify a project before you apply. However, if you would like to talk about research topics available in the lab please get in touch with Rob.
Projects are available for Masters or rotation students wanting to start in Spring 2023. please contact Rob for further details.