PhD Studentship: How Hematopoietic Transcription Factors and Epigenetic Coregulators Shape Gene Regulatory Networks in Immune Cell Development

This is a 4-year PhD studentship to join the group of Dr Tianyi Zhang in the Department of Cancer and Genomics Sciences at the University of Birmingham. This is a competition funded PhD through the Midlands Integrative Biosciences Training Partnership and is open to UK, EU, and International students.

Project
Transcription factors (TFs) and epigenetic coregulators cooperate to drive gene expression programmes that control cellular development. Ikaros is a hematopoietic TF that plays an essential role in the development of B cell and T cells, white blood cells that are crucial for healthy immune function. Ikaros also acts as a tumour suppressor that is highly mutated in progenitor B and T-cell acute lymphoblastic leukemia. Previous proteomic and functional biochemical studies from the lab have mapped key Ikaros partners, including the NuRD chromatin remodeller and HDAC complex, factors involved in the formation of repressive heterochromatin, SWI/SNF chromatin remodellers, and HAT coactivators. Several of these novel TF-coregulator molecular interfaces have been elucidated, while others remain to be identified. Moreover, mechanisms of how TFs such Ikaros direct the epigenetic activity of different coregulators to genomic targets with spatial-temporal precision during cellular differentiation remains poorly understood.

The aim of this PhD programme is to 1) uncover the molecular interfaces that mediate these key interactions 2) dissect how Ikaros partners with epigenetic coregulators to shape the chromatin landscape and gene regulatory networks 3) determine the impact of different Ikaros mutants in immune cell development in an vivo zebrafish model. This research project will reveal the molecular workings of a key driver of immune cell development, and in later years explore how other TFs cooperate with Ikaros or utilise similar mechanisms to exert their gene-regulatory functions.

Jointly supervised by Dr. Tianyi Zhang and Dr. Rui Monteiro, this project will provide comprehensive training in biochemistry, molecular biology, proteomics, genomics, and the use of cellular, cancer, and zebrafish model systems. The PhD student will be embedded in a broader research programme supported by Wellcome Trust funding.

Applicants should have a first-class or upper second-class honours undergraduate degree, a Master’s degree and/or relevant research experience in areas including biochemistry, molecular biology, genetics and bioinformatics. Proven research track record appropriate to career stage, strong analytical ability, communication skills and enthusiasm for collaborative research is essential. We are committed to building a diverse and inclusive research community, and welcome applications from talented candidates from all backgrounds regardless of age, disability, ethnicity, gender identity, religion, sexual orientation, or socioeconomic background.

To Apply:

Informal enquires with CV should be made to Dr Tianyi Zhang (t.zhang.9@bham.ac.uk)

Application link for this project:
https://admissions.bham.ac.uk/applicant-home/applications/courses/coursedetails/?programmeid=b3dfb4b3-6c66-ed11-9561-0022481b5835

Guidance on application:
https://www.birmingham.ac.uk/about/college-of-life-and-environmental-sciences/midlands-integrative-biosciences-training-partnership

Funding notes:

This is a competition funded PhD through the Midlands Integrative Biosciences Training Partnership and open to UK, EU, and International students. The studentship covers UK tuition fees and a stipend at the standard UKRI rate. International students at the University of Birmingham have the fee difference covered by university funding. Information about funding and the application procedure can be found here: https://www.birmingham.ac.uk/about/college-of-life-and-environmental-sciences/midlands-integrative-biosciences-training-partnership