1) Lipid droplet induction due to CIDE proteins
The study of factors that control lipid storage in different tissues is essential for understanding and controlling metabolic disorders. Cellular lipid storage is determined by a group of proteins that coat lipid droplets and facilitate storage or utilisation by regulation of metabolic processes. In mammalian cells, these lipid-coating proteins are members of the PAT (perilipin-ADRP-TIP47) domain family, which include perilipin, ADRP (or adipophilin), TIP47, S3-12 and MLDP/OXPAT. Recently, additional proteins, including CIDEA by our own investigations, have been discovered to have important roles in lipid droplet formation and function. We found that CIDEA can induce lipid droplets in non-adipocyte cells and is localized on the surface of these organelles. We are investigating the regulation and in vivo roles of CIDEA and the related proteins CIDEB and FSP27 in lipid accumulation.
2) Characterising the temperature dependent switch from white to brown adipocytes
As part of the DIABAT consortium (www.diabat.org) we are defining the genes that promote brown fat induction, transdifferentiation and activation of the energy expenditure program will provide new applications for combating the obesity epidemic. We aim to (i) determine the factors and pathways that define the switch from WAT to BAT-like adipocytes following cold exposure and (ii) identify the genes and pathways that discriminate WAT and BAT depots. As visceral WAT is considered significantly more detrimental to metabolic health in comparison to subcutaneous WAT (iii) we are also characterizing the pathways and genes that discriminate these two white fat depots.
3) The role of fatty acid signalling in adipocyte biology
Dietary fat has been correlated with obesity since it induces the proliferation and differentiation of pre-adipocytes. However it has become clear that the effect of fat on human health depends on the composition and the nature of fatty acids. We are studying intracellular signalling and G protein-coupled receptor signalling mediated by fatty acids in adipocyte cell systems.
4) The importance of microRNAs in endometrial differentiation
MicroRNAs (miRNAs) are genomically encoded, small, non-coding RNAs that regulate gene expression by controlling translation or stability of mRNAs. There are greater than 400 miRNAs identified, many of which display tissue specific expression patterns. They are key components in the regulation of developmental events and are required for cell fate specification and differentiation. During the menstrual cycle, ovarian estradiol and progesterone stimulate the ordered growth and differentiation of endometrial tissue compartments. We are studying microRNAs and their target genes involved in decidualization of human endometrium, defining their roles in regulating decidual cell function and examining if aberrant microRNA expression is associated with reproductive failure.