Passing on fat: regulation of membrane contact sites between organelles

Details

In order to utilise nutrients efficiently our cells need to take up lipids and store them for times when energy is sparse. Within our cells lipids are stored in special organelles, called ‘lipid droplets’. While almost all cell types in our body have the capacity to form lipid droplets, most lipids are stored in adipocytes (fat tissue) and hepatocytes (liver cells). Crucially, misregulation in the storing and utilisation of lipids leads to a range of diseases, such as obesity, lipid storage and non-alcoholic fatty liver disease.

For lipids to be broken down and used as energy supply, they must be passed on to other organelles, such as mitochondria and peroxisomes. It is therefore important to gain a better understanding of how lipids are transferred from one organelle to another in order to better combat these diseases. Importantly, this process of transporting lipids occurs through the formation of direct contact sites between organelles. However, little is understood about the regulatory mechanisms that control the formation of these contacts. This project is aimed at gaining a better understanding of how contact sites between lipid droplets and other organelles are regulated.

The key hypothesis in this project is that the formation of contact sites is regulated by unique changes to the membrane identity of organelles. This membrane identity is determined in part by phosphoinositides, a small family of interconvertible phospholipids. Lipid droplet contact sites offer the perfect opportunity to test this hypothesis. Through a unique combination of cell biological perturbation, discovery approaches, and in vitro reconstitution, you will gain a mechanistic and regulatory understanding of phosphoinositide identity changes during membrane contact site formation. The outcome of this approach will be a framework towards understanding the regulation of contact site formation and how lipids are transferred between organelles. This will form the basis for a better understanding of fundamental aspects in cell biology with profound implications to health and disease.

As part of this PhD project you will gain expertise in multiple cutting-edge techniques including:

• Fluorescence and electron microscopy

• Protein and membrane reconstitution

• Tissue culture of multiple cell lines

• Generation of knock-out and knock-in cells

The project will take place in the newly established lab of Dr. Maib, supported by a Wellcome Trust Fellowship. For any inquiries, please contact [email protected]

The project is only open to UK nationals.

Science Graduate School

As a PhD student in one of the science departments at the University of Sheffield, you’ll be part of the Science Graduate School. You’ll get access to training opportunities designed to support your career development by helping you gain professional skills that are essential in all areas of science. You’ll be able to learn how to recognise good research and research behaviour, improve your communication abilities and experience the breadth of technologies that are used in academia, industry and many related careers. Visit http://www.sheffield.ac.uk/sgs to learn more.

First class or upper second 2(i) in a relevant subject. To formally apply for a PhD, you must complete the University’s application form using the following link: http://www.sheffield.ac.uk/postgraduate/research/apply/applying

All applicants should ensure that both references are uploaded onto their application as a decision will be unable to be made without this information.