Exploring the therapeutic potential of targeting post-transcriptional gene regulation in blood cancers

About the Project

Proteins involved in post-transcriptional gene regulation play a pivotal role in carcinogenesis and cancer cell growth. Examples include components of the Ccr4-Not complex (which mediate shortening of the mRNA poly(A) tail), the BTG1 and BTG2 proteins (which bind poly(A)-binding protein and the Ccr4-Not complex), and the YTH family of proteins (which bind RNA containing methylated adenosine (m6A) residues). These proteins are linked with a variety of blood cancers including non-Hodgkin lymphoma (NHL), acute myeloid leukaemia (AML) and chronic lymphocytic leukaemia (CLL).

The project builds on our long-standing interest in post-transcriptional gene regulation and drug discovery. Depending on your preferences, the project can take one of two main directions:

(1) Functional analysis of key proteins involved in haematological malignancies using biochemical and cellular approaches.

(2) The discovery, development and characterisation of drug-like inhibitors of enzymes involved in post-transcriptional gene regulation.

Hosted within the Division of Biomolecular Science and Medicinal Chemistry of the School of Pharmacy, the project offers a multidisciplinary environment that bridges molecular and structural biology, biochemistry and assay development, molecular pharmacology and medicinal chemistry. Depending on your interest, the project can focus on cell-based assays, protein structure and biochemistry, the discovery of drug-like compounds, or medicinal chemistry. You will be able to develop skills that are an excellent preparation for a variety of careers in academia or industry.

The School of Pharmacy is one of the best universities in the subject area of pharmacy and pharmacology (Top-12, QS World Rankings 2025). You will join a vibrant community of postgraduate researchers thriving in an international, diverse, and intellectually stimulating research environment.

This project is open for self-funded students only. If you are a student from the EU or other parts of the world, please get in touch at an early stage to discuss possible funding opportunities.

References

References (3):
Kaur I, Jadhav GP, Fischer PM, and Winkler, GS (2024) Discovery of substituted 5-(2-hydroxybenzoyl)-2-pyridone analogues as inhibitors of the human Caf1/CNOT7 ribonuclease. Molecules 29, 4351; doi: 10.3390/molecules29184351
Ameerul A, Almasmoum H, Pavanello L, Dominguez C, and Winkler GS (2022) Structural model of the human BTG2–PABPC1 complex by combining mutagenesis, NMR perturbation data and molecular docking. Journal of Molecular Biology 434:167662
Almasmoum H, Airhihen B, Seedhouse C, and Winkler GS (2021) Frequent loss of BTG1 activity and impaired interactions with the Caf1 subunit of the Ccr4-Not deadenylase in non-Hodgkin lymphoma. Leukemia and Lymphoma, 62:281-290. doi: 10.1080/10428194.2020.1827243