Award details

Trafficking, storage and timely release of lipids: unfolding the fundamental mechanisms underlying metabolic reprogramming in pluripotent stem cells.

Reference	BB/P005209/2
Principal Investigator / Supervisor	Dr Mark Christian
Co-Investigators / Co-Supervisors
Institution	Nottingham Trent University
Department	School of Science & Technology
Funding type	Research
Value (£)	161,390
Status	Completed
Type	Research Grant
Start date	20/10/2019
End date	02/02/2022
Duration	28 months

Abstract

unavailable

Summary

unavailable

Impact Summary

The impact of this research will come from the advancement of knowledge in mechanisms of metabolic remodelling coordinating stem cell pluripotency and differentiation. This will have a major impact for diverse groups and applications in several ways: 1-Basic research underpinning health: the proposed research has potential medical implications in two main fields aimed at enhancing the quality of life and nation's health. (1) Regenerative medicine: the research will advance our understanding of how lipid storage impacts on pluripotent cell 'fitness' and developmental potency. Metabolic remodelling is directly relevant to reprogramming of somatic cells from patients and re-directing their fate to a desired cell type for stem cell-based therapies. (2) Reproductive medicine: elucidating how metabolic rewiring impacts the formation of pluripotent and extraembryonic tissues in the implanting embryo is of high significance. Understanding early changes in energy substrate usage will impact on standard culture procedures to maximise embryos viability for assisted reproduction. Maternal nutrition also has the potential to impact the foetus through changes in stem cell fate. Although the effects of maternal starvation on foetal stem cells are not known, in utero changes in metabolism are likely to impact on these cells and tissues that develop from them. 2-Innovative healthcare solutions: There are evident parallels in the metabolic pathways utilised by pluripotent and human cancer cells. Increased lipid droplet numbers have been described in tumours, however its functional significance remains to be determined. Our research will provide novel insights into the biology and dynamics of lipid droplets that will facilitate the future development of novel lipid droplet-targeted therapies applicable to cancer treatment and other diseases related to lipid storage (e.g. obesity). 3-Biotechnology and Industry: The proposed experimental approaches integrating information from metabolomics, genomics, proteomics and high-throughput functional screenings will disclose key metabolic pathways in stem cells that are potentially druggable, opening possibilities for collaboration with industrial partners. 4-Replacement of animal model: The stem cell systems and basic knowledge developed by this research will enable study of the metabolic rewiring implications in development in vitro and thus could be used to replace conventional animal-based models. 5-UK international competitiveness: this program of research will contribute to deliver the BBSRC's mission especially the strategic research priority 3 - Bioscience for Health as well as supporting the general UK strategy for excellence in stem cell research. 6-Education and training: This research contributes towards maintaining the standards of academic excellence at Imperial and Warwick. It will impact on our departments to offer educational opportunities for undergraduate and post-graduate student training. This is a multidisciplinary project involving groups with renowned expertise in developmental and stem cell biology, gene regulation, metabolism, lipid droplet proteomics, metabolic profiling, photonic microscopy and in vivo physiology. Researchers will receive specific scientific and technical training in partner labs as well as foster transferable professional, analytical and communication skills, facilitating their development and future prospects. 7-Science communication: the conceptual advances and material (e.g. pictures and illustrations) generated to present results will be used during outreach and fund raising activities with charities such as Genesis Research Trust. We will raise awareness of advances in the fields of reproductive biology, cell metabolism and regenerative medicine amongst diverse audiences. The pathway towards academic impact will be based on publications in open access high impact journals and presentations at international scientific meetings.

Committee	Research Committee C (Genes, development and STEM approaches to biology)
Research Topics	Stem Cells
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

Associated awards:

BB/P005179/1 Trafficking, storage and timely release of lipids: unfolding the fundamental mechanisms underlying metabolic reprogramming in pluripotent stem cells.

BB/P005209/1 Trafficking, storage and timely release of lipids: unfolding the fundamental mechanisms underlying metabolic reprogramming in pluripotent stem cells.

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