Cell biology during stress response. Bio-imaging and omics approaches for studying Ageing.

Mitochondria are essential for overall cell health as they provide the most efficient source of ATP via  oxidative phosphorylation.  During the lifetime of a cell, mitochondria encounter a range of bioenergetic and metabolic challenges but a number of pathways enable mitochondrial remodelling in order to meet cellular needs.  Part of the regulation involves fusion of individual mitochondria to form an interconnected network that is more energetically efficient and resilient.  On the other hand, as mitochondria become damaged through stress or age, mitochondrial networks are disassembled via fission to form small fragments that can be targeted for degradation via the autophagy / mitophagy pathway.  This dynamic balance of fusion, fission and mitophagy is critical to maintain a healthy pool of mitochondria and slow deterioration of this pathway is proposed to be a central component towards ageing.

Our long interest has been on the regulation of the autophagy pathway through ULK1 signalling which functions downstream of the central nutrient sensors, MTORC1 and AMPK.  ULK1 is needed to drive mitophagy but also has been proposed to regulate mitochondrial fission, placing this regulatory pathway at a critical decision point.  Our on-going work has identified novel ULK1 mechanism linking cell nutrients to mitochondrial maintenance. This PhD project will continue the line of work by characterising the cellular components transmitting these signals.

https://spider.science.strath.ac.uk/ChanLab/

Contact:   Edmond.Chan@strath.ac.uk

Molecular cell biology and CRISPR gene-targeting, 

Confocal and super-resolution imaging, proteomic analyses,  Cell signalling, biochemistry.

Chan, E. Y. (2012). Regulation and function of uncoordinated-51 like kinase proteins. Antioxid Redox Signal, 17(5), 775-785. doi:10.1089/ars.2011.4396.   http://www.ncbi.nlm.nih.gov/pubmed/22074133

Gallagher, L., Williamson, L. and Chan, E. (2016). Advances in Autophagy Regulatory Mechanisms. Cells, 5(2), 24.   http://www.mdpi.com/2073-4409/5/2/24

Gomes, L. C., Di Benedetto, G. and Scorrano, L. (2011). During autophagy mitochondria elongate, are spared from degradation and sustain cell viability. Nat Cell Biol, 13(5), 589-598. doi:10.1038/ncb2220.  

McAlpine, F., Williamson, L. E., Tooze, S. A. and Chan, E. Y. (2013). Regulation of nutrient-sensitive autophagy by uncoordinated 51-like kinases 1 and 2. Autophagy, 9(3), 361-373. doi:10.4161/auto.23066.   https://www.ncbi.nlm.nih.gov/pubmed/23291478

Mishra, P. and Chan, D. C. (2016). Metabolic regulation of mitochondrial dynamics. J Cell Biol, 212(4), 379-387. doi:10.1083/jcb.201511036.   https://www.ncbi.nlm.nih.gov/pubmed/26858267

Toyama, E. Q., Herzig, S., Courchet, J., Lewis, T. L., Jr., Loson, O. C., Hellberg, K., Young, N. P., Chen, H., Polleux, F., Chan, D. C. and Shaw, R. J. (2016). Metabolism. AMP-activated protein kinase mediates mitochondrial fission in response to energy stress. Science, 351(6270), 275-281. doi:10.1126/science.aab4138.   https://www.ncbi.nlm.nih.gov/pubmed/26816379