Dr Kate Poole is interested in how cells can "feel" their surroundings. Her research seeks to identify how cells sense and respond to changing mechanical inputs by identifying the molecules that can convert forces into electrical or biochemical signals that influence cell behaviour. Her research team is focused on two streams of research 1) characterising force sensing in cancer cells and 2) investigating what happens to our cells in microgravity (when the influence of Earth's gravity is ablated).
Force sensing in cancer cells
When solid tumours develop, there are many changes in the mechanical properties of both the cells and their surroundings. These mechanical changes can lead to a local stiffening of tissue around a tumour (as seen in the development of breast tumours, detected by feeling for lumps of stiffened tissue). This tissue stiffening can also promote progression of the disease. Our question is: what are the molecular force sensors in cancer cells that can sense and respond to these changes in mechanics? Our research has identified new force sensing molecules that influence cell migration and that may influence the initial steps of the metastatic cascade, where cancer cells break from a tumour mass and invade the surrounding tissue. We are currently working to understand precisely how these force sensors are activated and to identify the specific role of this mechanical signalling in the dissociation of cells from a tumour mass.
The impact of microgravity on cellular function
All life on Earth has evolved under the persistent pull of Earth's gravitational field. While life can be sustained in reduced gravity environments (such as the microgravity experienced on the International Space Station) there are significant disruptions in human physiology that have negative impacts on health and performance. These impacts on human health have been relatively well defined by studying the impact of extended stays in microgravity on astronauts but we do not yet know the mechanisms by which these changes occur. Kate's team are investigating how disruptions in force sensing and cellular structures can lead to changes in cellular function when cells are exposed to simulated microgravity. The overall goal of this work is to characterise how human health and performance is negatively impacted, at the molecular and cellular level, by reduced gravity environments, with the goal to identify ways to counter these negative effects, thus increasing human access to space.
K. Poole. Do mechanically activated ion channels enable cellular sensing of microgravity? AOARD (US Air Force), 21IOA035, 2021
K. Poole, K. Kilian, S. Sianati, N. Ariotti. Mechanosensors in Cancer NHMRC, APP1185021, 2020
K. Poole, B. Martinac, M. Biro, M. Baker. The role of force-sensing ion channels in melanoma migration NHMRC, APP1138595, 2018
K. Poole and B. Martinac. Mechanoelectrical Transduction in Chondrocytes, NHMRC, APP1122104, 2017
K. Poole. Cellular sensing of the physical environment, Helmholtz Association, Max Delbruck Center for Molecular Medicine, Cecile Vogt Fellowship, 2012
K. Poole and GR Lewin, Substrate directed polarisation of mechanotransduction domains in somatosensory neurons, German Research Council (DFG) SFB958, project A09, 2011
UNSW Arc Postgraduate Council Outstanding Research Supervisor Award
Silvani, G., Bradbury, P., Basirun, C., Mehner, C., Zalli, D., Poole, K. and Chou, J. Testing 3D printed biological platform for advancing simulated microgravity and space mechanobiology research npj Microgravity 8: 1-11 (2022)
Poole, K. The Diverse Physiological Functions of Mechanically Activated Ion Channels in Mammals. Annu Rev Physiol 84:307-329 (2022)
Patkunarajah, A*., Stear, J.H*., Moroni, M., Schroeter, L., Blaszkiewicz, J., Tearle, JLE., Cox, C.D., Fuerst, C., Sanchez-Carranza, O., del Angel Ocana Fernandez, M., Fleischer, R., Eravci, M., Weise, C., Martinac, B., Biro, M., Lewin, G.R., Poole, K. TMEM87a/Elkin1, a component of a novel mechanoelectrical transduction pathway, modulates melanoma adhesion and migration. eLife 9, e53308 (2020)
Bavi*, N., Richardson*, J., Heu, C., Martinac, B., Poole, K. PIEZO1-Mediated Currents Are Modulated by Substrate Mechanics. ACS Nano 13: 13545–13559 (2019).
Servin-Vences, M.R., Moroni, M., Lewin, G.R. Poole, K. Direct measurement of TRPV4 and PIEZO1 activity reveals multiple mechanotransduction pathways in chondrocytes. eLife 6, e21074 (2017)
My Research Supervision
Jessica Richardson (PhD student)