Obesity levels are rising rapidly around the world and are a major risk factor for diseases such as Type 2 diabetes, cancers and recently, COVID-19. New strategies and innovations are thus needed to prevent and treat obesity and associated disease. This requires an in-depth understanding of the genetic, cellular and physiological mechanisms underlying obesity.
In obesity, excessive expansion of adipose tissues leads to adipose dysfunction and increased risk for associated diseases. To identify regulators of adipose growth mechanisms, we have (i) leveraged genome-wide association studies on human obesity to identify novel genes regulating adipose expansion, and (ii) cross-referenced these candidate genes with metabolically healthy or unhealthy obesity.
In this PhD project, we will use the highly tractable Drosophila model system to gain a mechanistic understanding of how these candidate genes regulate adipose tissue expansion and thereby influence obesity.
The project aims to:
i) Use genetic data from humans to identify new genes that regulate growth of adipose tissue;
ii) Generate Drosophila models of candidate genes to gain insights into their mechanistic role in adipose tissue expansion;
iii) Understand how these candidate genes function in the adipose tissue in Drosophila exposed to an obesogenic diet and
iv) Identify new mechanisms that regulate adipose expansion and dysfunction in obesity.
We will use a variety of methodological approaches in this project, including: genetic analysis, immunohistochemistry, confocal and light sheet in vivo microscopy, biochemical and metabolic assays, Drosophila nutritional assays and molecular biology techniques (including the use of CRISPR/Cas9 tools).
The supervisor team has extensive experience and expertise in studying the Drosophila adipose tissue (Agrawal et al., 2016; Delanoue et al., 2016) and utilising human genetics to model adipose expansion genes (Loh et al., 2020).
We welcome discussions with prospective students and anticipate that the final project will be designed incorporating the student’s interests.
https://www.ed.ac.uk/profile/neha-agrawal
https://www.research.ed.ac.uk/portal/en/persons/james-minchin(284e253e-2cb1-412a-acad-8423df06637b).html
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