Primary Supervisor: Dr Iain Macaulay - firstname.lastname@example.org
Secondary Supervisor: Wilfried Haerty (EI)
Aneuploidy, the state in which cells exhibit abnormal chromosomal copy number is the leading cause of miscarriage and congenital defects in humans and is common in many cancers. Gains or losses of chromosomes occur in individual cells, where they can directly impact gene expression, cell phenotype and function, and ultimately, the health of the organism.
In this project, we seek to understand the impact that gains and losses of chromosomes can impact gene expression in individual cells. We have previously shown that cells harbouring additional chromosomes have changes in gene expression arising from both the "gained" chromosome but also throughout the genome. It is this combination of cis- and trans- effects of aneuploidy we wish to study, at scale, in this project. Furthermore, the student will also explore instances of programmed polyploidy - investigating how the massive gains of chromosome copy number seen in megakaryocytes - large bone marrow cells which make platelets - can influence gene expression and terminal differentiation of these cells. Using a range of technologies, including cell sorting (FACS) and subcloning, single-cell multiomics and next-generation sequencing and bioinformatics, the student will build a library of aneuploid human cells, confirming their aneuploid status by classical karyotyping and through single-cell genome sequencing. The student will, in parallel, generate transcriptomes for these cells using G&T-seq, thus building a detailed overview of how changes in chromosome copy number can impact gene and isoform expression throughout the genome. Based in the Macaulay lab at the Earlham Insititute and in collaboration with the Haerty and Nieduszinsky groups at EI the student will receive extensive training in experimental and computational biology, developing broad and transferrable expertise in cellular genomics.
The Norwich Research Park Biosciences Doctoral Training Partnership (NRPDTP) is open to the UK and international candidates for entry in October 2022 and offers postgraduates the opportunity to undertake a 4-year PhD research project whilst enhancing professional development and research skills through a comprehensive training programme. You will join a vibrant community of world-leading researchers.
All NRPDTP students undertake a three-month professional internship placement (PIPS) during their study. The placement offers exciting and invaluable work experience designed to enhance professional development. Full support and advice will be provided by our Professional Internship team. Students with, or expecting to attain, at least an upper second class honours degree, or equivalent, are invited to apply.
This project has been shortlisted for funding by the NRPDTP programme. Shortlisted applicants will be interviewed on Tuesday 25th January, Wednesday 26th January and Thursday 27th January 2022.
You can visit the Norwich Research Park Biosciences Doctoral Training Partnership pages for further information on eligibility and how to apply.
Our partners value diverse and inclusive work environments that are positive and supportive. Students are selected for admission without regard to gender, marital or civil partnership status, disability, race, nationality, ethnic origin, religion or belief, sexual orientation, age or social background.