The cancer genomes sequenced in the last decade revealed histone methyltransferases MLL2 (KMT2D) and MLL3 (KMT2C) as two out of the 10 most often mutated genes in cancers. Nevertheless, their protein functions in normal physiology and disease, including cancer, are largely unclear and just starting to be understood. We have previously shown that histone methyltransferase MLL2 has an essential role in gene expression and genomic maintenance1. More specifically, deletion or mutation of MLL2 results in transcriptional stress, mutations in specific genes and genomic instability1. We would now like to investigate the role of the sister protein MLL3 on gene expression and genomic maintenance, and compare the functions and contributions of both proteins to genomic and transcriptional homeostasis.
We will employ immortalised, inducible MLL3 knock-out (KO) mouse embryonic fibroblast (MEFs) cells to investigate the functions of MLL3 and compare them to those of MLL21. We will use a variety of approaches to answer the experimental questions, including cell biology, molecular biology, biochemistry and computational methods that we have previously established1–5.
By the completion of this project, we will acquire a better understanding of the MLL3 functions in normal cells and disease, as well as the interplay of MLL2 and MLL3 protein functions in cells. Considering that mutations in either MLL2 or MLL3 lead to genetic syndromes and promote carcinogenesis, the proposed work is bound to have a positive impact both on understanding the physiology of those genetic syndromes and the development of a broad range of cancers.
Person Specification
The applicants are required to have a minimum 2:1 BSc degree in a relevant discipline. A related MSc/MRes degree or/and research experience would be a plus.
Submitting an application
As part of the application, you will need to supply:
· A copy of your current CV
· Copies of your academic qualifications for your Bachelor degree, and Masters degree (if studied); this should include both certificates and transcripts, and must be translated in to English
· A research proposal statement*
· Two academic references
· Proof of your English Language proficiency
Details of how to submit your application can be found here.
*The application must be accompanied by a “research proposal” statement. An original proposal is not required as the initial scope of the project has been defined, candidates should take this opportunity to detail how their knowledge and experience will benefit the project and should also be accompanied by a brief review of relevant research literature.
Please include the supervisor’s name and project title in your Personal Statement.
If you require further information about the application process please contact the Postgraduate Admissions team at [Email Address Removed]