PROJECT IN BRIEF
This funded, 4-year PhD project addresses the fundamental question of how individual cells sense and respond to environmental changes. A particular focus is on the signalling mechanisms to orchestrate various biological processes occurring at diverse subcellular locations/compartments (“organelles”). Because improper cellular responses cause serious diseases including cancer, diabetes and Alzheimer’s, understanding the signalling process will contribute to develop therapeutic strategies against these diseases.
OBJECTIVES
This project will address how the Target of Rapamycin Complex 1 (TORC1, or mTORC1) kinase, the central regulator of cell growth, receives signals from, and sends signals to, diverse organelles. TORC1 enables cells to properly adapt to the changing environment (nutrient availability, growth factor signals, cellular stresses etc) by tuning numerous biological processes such as DNA transcription, protein synthesis, trafficking and degradation (“autophagy”), and lipid metabolism. The remarkable prevalence of TORC1’s function can be explained by the division of labour between its multiple pools, which we recently demonstrated using budding yeast model (Hatakeyama et al., 2019, Molecular Cell). Specifically, there exist one TORC1 pool localizing to the organelle called endosomes (E-TORC1) while the other to lysosomes (L-TORC1). Each of them regulates distinct processes via phosphorylating distinct proteins. Based on this finding, the PhD project aims to address the following questions:
1. How are E- and L-TORC1 regulated?
2. How does TORC1 signal beyond endosomes and lysosomes?
A long-term goal is to apply the knowledge to better treat cancer, diabetes and neurodegenerative diseases by selectively targeting desired subsets of TORC1 functions.
APPROACHES
This project combines a broad range of techniques in genetics (e.g. genome editing), biochemistry (e.g. protein purification, kinase assay, proteomics), cell biology (e.g. microscopy) and bioinformatics. Our lab uses two model systems: budding yeast and mammalian cultured cells. The yeast system allows swift acquisition of solid data leading to fundamental discoveries. The translational potential of the discoveries will be immediately tested using mammalian cells. Unique to our lab is the molecular tools to specifically measure or manipulate E- and L-TORC1 activities, which allows us to study the two pools separately. Using these experimental tools and bioinformatic approaches, we have identified novel factors (proteins and chemicals) that regulate, or are regulated by, TORC1 at endosomes, lysosomes or other organelles. The underlying molecular mechanisms will be investigated in this project.
ENVIRONMENT
Our lab is situated in the Institute of Medical Sciences (IMS) of the University of Aberdeen. The student will benefit from IMS’s excellent core facilities including various fluorescence and confocal microscopes and mass spectrometers with technical supports. The student will be trained through a close supervision by the freshly appointed group leader. The student will frequently communicate with neighbouring labs in IMS through regular joint lab meetings and learn a broad range of subjects in cell biology, genetics, and cancer biology. In addition, there will be opportunities to discuss the translational aspect of the project with experts in cancer, diabetes and neurological research across IMS. Moreover, the student will have chances to interact with national and international collaborators in Europe (including UK, Switzerland, Germany, Belgium and Spain), USA and Japan, to expand his/her professional network for future career development.
Informal enquiries would be welcomed for a discussion. Please contact Dr Riko Hatakeyama ([Email Address Removed]) for more information.
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This project will be based within the Institute of Medical Sciences (IMS), part of the School of Medicine, Medical Sciences and Nutrition, at the University of Aberdeen. The IMS is located on the Foresterhill Health Campus, one of the largest clinical complexes in Europe, which also includes the Institute of Applied Health Sciences, a large teaching hospital and the Rowett Institute of Nutrition and Health.
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APPLICATION PROCEDURE:
International applicants are eligible to apply for this studentship but will have to find additional funding to cover the difference between overseas and home fees (approximately £18,000 per annum)
- Formal applications can be completed online: https://www.abdn.ac.uk/pgap/login.php
- You should apply for Medical sciences PhD to ensure your application is passed to the correct team.
- Please clearly note the name of the supervisor and exact project title on the application form. If you do not mention the project title and the supervisor on your application it may not be considered for the studentship.
- Candidates should have (or expect to achieve) a First Class Honours degree (or Equivalent) in a relevant subject. Applicants with a 2:1 Honours degree may be considered provided they have a Distinction at Masters level.
- Please include a personal statement, an up-to-date copy of your academic CV, and your relevant educational certificates and transcripts.
- Please note: you DO NOT need to provide a research proposal with this application.
- General application enquiries can be made to [Email Address Removed]
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