Funding providers: Cancer Research Wales
Subject areas: Drug discovery / Medicinal chemistry/ Leukaemia /Anticancer
Project start date:
- 1 October 2023 (Enrolment open from mid-September)
Project supervisors:
Aligned programme of study: PhD in Medical and Health Care Studies
Mode of study: Full-time
Project description:
The Swansea University School of Medicine hosts a world-leading research programme in drug discovery and anticancer research. Medicinal chemistry plays a pivotal role in a wide range of aspects of drug discovery and development, offering many opportunities for interdisciplinary research. This research project, funded by Cancer Research Wales, runs in collaboration with the School of Pharmacy and Pharmaceutical Sciences and the European Cancer Stem Cell Research Institute, both at Cardiff University, and aims to identify and develop novel inhibitors of GATA2, as an innovative approach to target leukaemia blasts and stem cells in therapy-resistant acute myeloid leukaemia (AML). AML is an aggressive blood cancer where myeloid progenitors are blocked in their ability to differentiate into specialised myeloid blood cells, instead generating immature abnormal blast cells that competitively suppress the ability of the bone marrow to produce these and other blood cell types. Annually, around 2,700 deaths from AML occur in the UK, accounting for 2% of all UK cancer deaths. AML is treated with a combination of high-dose induction chemotherapy, to kill proliferating leukaemia blasts, and a consolidation chemotherapy, to keep the leukaemia at bay for an extended period. Unfortunately, for most patients afflicted with AML, treatments are largely non-specific and toxic, targeting leukaemia and normal cells alike, and ineffective at eliciting cure.
The quest to develop more specific, targeted therapies for AML has been impaired by the presence of leukaemia stem cells/initiating cells (LSCs), which are the root cause of AML, enabling AML cells to prosper, and which resist standard chemotherapy treatments, ultimately causing relapse. We have addressed this issue by focusing on understanding the oncogenic function of the haematopoietic specific transcription factor GATA2, which is overexpressed across several subtypes of AML. Our preliminary data collectively suggest the potential of targeting GATA2 in AML blast cells and, more specifically, in AML LSCs.
In this project, a combination of computer-aided drug design techniques (molecular modelling), synthetic organic chemistry methods and biological assays will be used to identify, synthesise and develop novel and selective small-molecule GATA2 inhibitors, able to target both leukemic blast cells and propagating LSCs, as potential treatments for therapy-resistant AML. Research on GATA2 as a target for AML is still at a very early stage, therefore this project has potential for a significant social and scientific impact worldwide.
Starting from an hit molecule we recently identified, a series of in silico analyses will guide the design and synthesis of novel structural analogues, which will be synthesised and then evaluated in a series of biological assays.
Modern laboratories and state-of-the-art equipment will be available to support this research and offer unique training opportunities.
Excellent candidates with a background in medicinal/organic chemistry, drug discovery, or closely related disciplines (Chemistry, Medicinal Chemistry, Pharmaceutical Chemistry or Biochemistry) are strongly encouraged to contact Dr Salvatore Ferla ([Email Address Removed]) to learn more about the project and the multidisciplinary training opportunities available to the successful applicant.
Eligibility
Candidates must have a First, Upper Second Class Honours or a master’s degree with Merit, in a relevant discipline (Chemistry, Medicinal Chemistry, Pharmaceutical Chemistry or Biochemistry).
English Language requirements: If applicable – IELTS 6.5 overall (with at least 5.5 in each individual component) or Swansea recognised equivalent.
Due to funding restrictions, this scholarship is open to applicants eligible to pay tuition fees at the UK rate only, as defined by UKCISA regulations.
Continue with Facebook
