Our Institute has an international reputation for cancer research, with world renowned experts in the field.
As part of our comprehensive training programme, fully funded by Cancer Research UK, we have funding for 3 PhD studentships to commence in September 2021.
Our training programme aims to develop a cohort of scientists equipped both intellectually and technically to conduct the highest quality research on cancer.
Our research degrees are supplemented by a comprehensive support programme, providing training in a wide range of biomedical laboratory methods and other vital transferable skills.
We are now inviting applications for the following projects:
First Supervisor: Dr Faraz Mardakheh
Second supervisor: Dr Andrew Finch
KRAS is amongst the most commonly mutated oncogenes in human cancers. It has been known for a long time that KRAS signalling regulates gene expression transcriptionally, via modulating the activity of key downstream transcription factors such as MYC. However, how KRAS impacts on gene expression post-transcriptionally, after RNA is synthesised from DNA, is unclear. RNA Binding Proteins (RBPs) are the main post-transcriptional regulators of gene expression, determining all aspects of an RNA life-cycle regulation from transcript processing and stability to transport and translation. Using a novel proteomics approach, we have recently revealed that KRAS oncogene can modulate the RNA binding activity of several RBPs, some of which are crucial for malignancy. Focusing on one such crucial RBPs, a nucleolar protein named Nucleolin (NCL), the aim of this project is to mechanistically understand how KRAS regulates NCL association with RNA targets, how NCL functions downstream of KRAS to promote malignancy, and whether this pathway can be targeted therapeutically in Pancreatic Ductal Adenocarcinoma, a highly aggressive cancer of unmet needs in which KRAS mutations are present in more than 90% of the cases.
First Supervisor: Prof Kamil R Kranc
Second Supervisor: Dr Lovorka Stojic and Prof Donal O’Carroll
Acute myeloid leukaemia (AML) is a clonal disorder of haematopoietic stem/progenitor cells, which acquire mutations to form leukaemic stem cells (LSCs) that fuel the disease. Since current therapies fail to eradicate disease-causing LSCs, which also fuel devastating disease relapses, it is essential to identify therapeutic targets for LSC elimination. Significantly, emerging research has placed RNA modifications as key regulators of cancer formation. In fact, our studies revealed that mRNA N6-methyladenosine (m6A) modification, whose function is executed by the m6A reader YTHDF2 that promotes mRNA decay, plays an essential role in AML, specifically compromising LSCs (Paris et al, Cell Stem Cell, 2019). Moreover, we also discovered that deletion of uridylyl-transferases which uridylate mRNA polyA tails, thus promoting their decay, disables LSCs. Therefore, inhibition of YTHDF2- and uridylation-mediated RNA degradation may offer unprecedented therapeutic value in treating AML.
We hypothesise that uridylation- and m6A-depended RNA decay pathways are promising therapeutic targets in AML. Firstly, we will reveal whether targeting uridylation eliminates LSCs. Secondly, we shall dissect the mechanisms through which uridylation may drive AML propagation. Finally, we will determine whether uridylation and YTHDF2 control overlapping or distinct transcripts for degradation, and reveal the novel therapeutic value of their inhibition in AML. This project will unveil and functionally explore the translational potential of inhibiting mRNA decay pathways to specifically eradicate LSCs.
First Supervisor: Dr Miguel Ganuza
Second Supervisor: Dr Bela Wrench
Despite recent advances, the treatment outcomes for adults with acute lymphoblastic leukaemia (ALL) are poor. Although they initially respond well and the bulk of tumour cells is eliminated following chemotherapy, most adult patients undergo clinical relapse. This highlights the existence of a subset of ALL leukaemia cells which survive to chemotherapy and regenerate the disease. Cellular and molecular interactions between leukaemia cells and other cellular components that form the bone marrow (BM) niche are emerging as critical players during this process. Our results indicate that chemotherapy induces the evolution of the adipocyte population within the BM niche and moreover that these therapy emergent adipocytes constitute a key mechanism of cancer treatment interference. This project aims to dissect at the single cell level the particular cellular components (including adipocyte subtypes) which specifically interact with ALL cells at different stages during disease and how this composition changes upon chemotherapy. Moreover, this research will molecularly unveil how adipocyte evolution induces ALL cells to enter quiescence and low translation states, traits that abrogate chemotherapeutic effects. This project holds the promise to open new avenues for ALL treatment based on the identification of novel therapeutic niche-based targets that could reduce dormancy in chemotherapy-resistant ALL cells.
Useful information about these studentships and the application process:
Academic Entry Requirements
All applicants should have or be expecting:
If your degree has not yet been awarded but you are expected to meet the above entry requirements, you are welcome to apply.
For more information on international equivalencies please see here.
English Language Requirements
Applicants for whom English is not a first language will also require a minimum IELTS score of 6.5 (with 6.0 in the written component), or equivalent, unless your undergraduate degree was studied in, and awarded by, an English speaking country. For more information on acceptable English language qualifications please see here.
Please note that funding for these fellowships is only provided at the Home rate.
The funding for this studentship only covers tuition fees at the Home rate. Overseas applicants are welcome to apply, but they will be required to fund the difference in tuition fees.
These studentships include the following funding for 3 years:
Part-time students will receive pro-rata funding for 6 years.
You will need to complete our online application form. You will be required to include the following as part of your application:
When completing the application form, please ensure that:
If you have a question about a specific project, please contact the supervisor directly. For general enquiries about the PhD studentship or application process please contact firstname.lastname@example.org
Successfully shortlisted candidates will be invited to an interview at Barts Cancer Institute.
We are in the process of securing the dates for the interviews (most likely during the week b/w 15 February 2021) and will publish them here once they have been confirmed.