Abstract
Recent evidence suggests that liquid-liquid phase separation processes physically define key structures within the nucleus. This studentship will investigate the role of biomechanical forces in nuclear phase separation. Experimental studies in the primary supervisor’s laboratory will employ engineered surfaces to control the cell’s mechanical environment and opto-genetic reporters to analyse the formation of biomolecular condensates. This work will be complemented by computational modelling of nuclear biophysics supported by the secondary supervisor. Together, these studies will provide new insights into the biophysical regulation of nuclear architecture, and the student will gain outstanding interdisciplinary training at the interface between physics and biology.
References
Shin Y, Brangwynne CP. Liquid phase condensation in cell physiology and disease. Science, 2017; 357(6357).
Bracha D, Walls MT, Wei MT, Zhu L, Kurian M, Avalos JL, Toettcher JE, Brangwynne CP. Mapping local and global phase separation behavior using photo-oligerizable seeds. Cell, 2018; 175(6).
Connelly JT, Gautrot JE, Trappmann B, Tan DW, Donati G, Huck WTS, Watt FM. Actin and serum response factor transduce physical cues from the microenvironment to regulate epidermal stem cell fate decisions. Nature Cell Biology, 2010; 12(7).
Laly AC, Sliogeryte K, Pundel OJ, Ross R, Keeling MC, Avisetti D, Waseem A, Gavara N, Connelly JT. The keratin network of intermediate filaments regulates keratinocyte rigidity sensing and nuclear mechanotransduction. Science Advances, 2021; 7(5).
Hafner AE, Gyori NG, Bench CA, Davis LK, Saric A. Modelling fibrillogenesis of collagen mimetic molecules. Biophysical Journal, 2020; 119(9).