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  Investigating fatty acid metabolism in acute leukaemia (RUSHWORTHS_U23FMH)


   Norwich Medical School

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  Dr S Rushworth  No more applications being accepted  Competition Funded PhD Project (Students Worldwide)

About the Project

Background   

AML is a highly lethal disease in which the overall survival rate has not improved over the last 25 years. AML is primarily a disease of the elderly with three quarters of patients diagnosed after the age of 60 and presently the majority of patients with acute myeloid leukaemia (AML) die within a year of diagnosis. Increasing doses, or variations of cytotoxic chemotherapy regimens, have been trialled in recent decades but without success and accordingly it is envisaged that novel approaches to treating AML, informed by an improved scientific understanding of the disease, will be needed to improve outcomes for patients in the future 

Research methodology 

To gain a better understanding of the mechanisms regulating AML in the context of its local bone marrow but also the wider organ system will enable us to propose strategies for therapeutic intervention. Therefore, the aim of this project is to define the metabolic mechanisms underpinning AML progression. Specifically, we will determine the role of various metabolic regulators in these processes.  To do this, the PhD student will learn in vivo techniques including animal handling, as well as isolation of primary cells for functional characterisation. The student will receive training in cellular biology methodologies including, analysis of nucleic acids by qPCR and proteins by western blot, ELISA and immunohistochemistry. The student will also learn to characterise and isolate AML by FACS. 

Training 

The project will be carried out under the supervision of Dr Rushworth (Norwich Medical School). I have successfully supervised seven PhD students who immediately left for post-docs. Our lab is a supportive and collaborative environment, holds weekly lab meetings, biweekly journal club and encourages presentation at local, national and international meetings. Training provided will lead to the development of advanced research skills as well as other generic transferable skills. 


Biological Sciences (4)

Funding Notes

This PhD project is in a Faculty of Medicine and Health Sciences competition for funded studentships. These studentships are funded for 3 years and comprise UK fees, an annual stipend of £17,668 and £1,000 per annum for research training (RTSG). Overseas applicants (including EU) may apply but are required to fund the difference between Home and International tuition fees.

References


Mistry JJ, et al. Free fatty-acid transport via CD36 drives β-oxidation-mediated hematopoietic stem cell response to infection. Nat Commun. 2021 Dec 8;12(1):7130.
Moore JA, et al. LC3-associated phagocytosis in bone marrow macrophages suppresses acute myeloid leukemia progression through STING activation. J Clin Invest. 2022 Jan 6:e153157.
Mistry JJ, et al. ROS-mediated PI3K activation drives mitochondrial transfer from stromal cells to hematopoietic stem cells in response to infection. Proc Natl Acad Sci U S A. 2019 Dec 3;116(49):24610-24619.
Shafat MS, et al. Leukemic blasts program bone marrow adipocytes to generate a protumoral microenvironment. Blood. 2017 Mar 9;129(10):1320-1332

Where will I study?