Dr M Ralser
No more applications being accepted
Funded PhD Project (Students Worldwide)
About the Project
This 4-year PhD studentship is offered in Dr Markus Ralser’s Group based at the Francis Crick Institute (the Crick).
Mitochondria are not the single-unit organelles as often depicted in the textbook, but can dynamically undergo fission and fusion depending on the physiological status of the cell. In budding yeast, a model for mitochondrial dynamics, all mitochondrial units do fuse together and form a single tubular network when nutrients are plentiful and cells grow exponentially. However, when nutrients are depleted, or when cells are exposed to stress conditions, like oxidants, heat, or toxins, the mitochondrial network disassembles (undergoes fission) and the individual mitochondrial units are restored. There are meanwhile several genes known that are important for mitochondrial networks to undergo fission and fusion, but its still largely unclear, how the cellular signals are incorporated so that this process controlled. Moreover, when cells grow together in communities, the status of the network can differ from cell to cell (one cell may have all mitochondria fused, while its neighbouring cell not) despite they have equal access to the same growth conditions. The status of the mitochondrial network hence reflects cell-cell heterogeneity in communities, the reason for this phenotype is unclear as well.
We have recently found evidence that nucleotide metabolism, in particular the biosynthesis of uracil, determines whether a cellular mitochondrial network is able to undergo fission when conditions change, and we have found that cells that cooperatively exchange uracil in a community, differ in their mitochondrial networks. In this project, the molecular mechanisms underlying this phenotype should be elaborated to gain an understanding about the source of cell-cell differences in mitochondrial dynamics. In practical terms, the experiments will involve super resolution microscopy in order to picture mitochondrial networks and how they change in stress situations, mass spectrometry to quantify metabolites and metabolic pathways involved, and techniques of molecular biology, in particular cloning and genome editing by CRISPR/Cas9, in order to elaborate the genetic mechanisms.
Talented and motivated students passionate about doing research are invited to apply for this PhD position. The successful applicant will join the Crick PhD Programme in September 2017 and will register for their PhD at one of the Crick partner universities (Imperial College London, King’s College London or UCL).
Applicants should hold or expect to gain a first/upper second-class honours degree or equivalent in a relevant subject and have appropriate research experience as part of, or outside of, a university degree course and/or a Masters degree in a relevant subject.
APPLICATIONS MUST BE MADE ONLINE VIA OUR WEBSITE BY 23:59 (UK TIME) on SUNDAY 26 MARCH 2017. APPLICATIONS WILL NOT BE ACCEPTED IN ANY OTHER FORMAT.
https://www.crick.ac.uk/about-us/jobs-and-study/phd-programme/
Funding Notes
Successful applicants will be awarded a non-taxable annual stipend of £22,000 plus payment of university tuition fees. Students of all nationalities are eligible to apply.
References
1. Campbell, K., J. Vowinckel, M. Muelleder, S. Malmsheimer, N. Lawrence, E. Calvani, L. Miller-Fleming, M. T. Alam, S. Christen, M. A. Keller and M. Ralser (2015)
Self-establishing communities enable cooperative metabolite exchange in a eukaryote.
eLife 4: e09943.
2. Vowinckel, J., J. Hartl, R. Butler and M. Ralser (2015)
MitoLoc: A method for the simultaneous quantification mitochondrial network morphology and membrane potential in single cells.
Mitochondrion 24: 77-86.
3. Alam, M. T., A. Zelezniak, M. Mülleder, P. Shliaha, R. Schwarz, F. Capuano, J. Vowinckel, E. Radmaneshfar, A. Krüger, E. Calvani, S. Michel, S. Börno, S. Christen, K. R. Patil, B. Timmermann, K. S. Lilley and M. Ralser (2016)
The metabolic background is a global player in Saccharomyces gene expression epistasis.
Nature Microbiology 1: 15030. PubMed abstract
4. Youle, R. J. and A. M. van der Bliek (2012)
Mitochondrial fission, fusion, and stress.
Science 337: 1062-1065.
5. Westermann, B. (2010)
Mitochondrial fusion and fission in cell life and death.
Nature Reviews Molecular Cell Biology 11: 872-884.