Tuning the senses

Kate Poole wants to understand how cells sense touch.

Molecular scale movements detected by sensory cells generate electrical signals translating into touch or pain. Exactly how this happens is still not clear.

To monitor cellular responses to ultrafine movements, Kate grows cells on top of microscopic elastic cylinders—a setup she developed with colleagues in Germany. 

Kate discovered that protein complexes spanning the membrane—linking the inside of the cell with the extracellular matrix—control sensory signals.

Electrical signals are generated in many cell types in response to mechanical stimuli. Being able to tune sensory signals provides a way to manage cartilage rebuilding, melanoma metastasis and other functions.

The sensing of and discrimination between different physical inputs is critical in the function of many cells and tissues in multicellular organisms; an acute response to mechanical stimuli underpins our senses of touch and hearing, integrated sensing of changing mechanical loads is fundamental for maintaining cartilage and the vasculature, and migratory cells (such as fibroblasts in wound healing or tumour cells during metastasis) can probe the mechanical properties of their surroundings by applying forces at cell-matrix contact points. Kate is studying the molecular mechanisms of cellular sensing of physical stimuli across a number of mammalian systems: in touch sensation in the somatic sensory system, the homeostatic maintenance of cartilage and in melanoma progression and metastasis.

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We are always looking for motivated students interested in mechanobiology and ion channels. Please get in touch if you would like to work with us on projects related to these topics.

About Kate Poole

Dr Kate Poole is an Associate Professor at UNSW's School of Medical Sciences. She received her PhD from the University of Adelaide (2002), and completed post-doctoral training in Germany: at Max Planck Institute for Molecular Cell Biology and Technische Universität Dresden, Dresden (2002-2005), and Max Delbrück Center for Molecular Medicine, Berlin (2008-2012). In between, Kate spent a couple of years working in industry for the Atomic Force Microscopy company, JPK Instruments, AG. She established her own research group in 2012 at the Max Delbrück Center in Berlin supported by a Cecile Vogt Fellowship. Kate returned to Australia in 2016 when she was recruited as a group leader in Single Molecule Science.

Select Publications

Beaulieu-Laroche L; Christin M; Donoghue A; Agosti F; Yousefpour N; Petitjean H; Davidova A; Stanton C; Khan U; Dietz C; Faure E; Fatima T; MacPherson A; Mouchbahani-Constance S; Bisson DG; Haglund L; Ouellet JA; Stone LS; Samson J; Smith MJ; Ask K; Ribeiro-da-Silva A; Blunck R; Poole K; Bourinet E; Sharif-Naeini R (2020) 'TACAN Is an Ion Channel Involved in Sensing Mechanical Pain', Cell, vol. 180, pp. 956 - 967.e17, http://dx.doi.org/10.1016/j.cell.2020.01.033

Patkunarajah A; Stear JH; Moroni M; Schroeter L; Blaszkiewicz J; Tearle JLE; Cox CD; Fuerst C; Sánchez-Carranza O; Fernández MDÁO; Fleischer R; Eravci M; Weise C; Martinac B; Biro M; Lewin GR; Poole K (2020) 'TMEM87a/Elkin1, a component of a novel mechanoelectrical transduction pathway, modulates melanoma adhesion and migration.', eLife, vol. 9, http://dx.doi.org/10.7554/eLife.53308

N. Bavi, J. Richardson, C. Heu, B. Martinac, K. Poole (2019) PIEZO1-Mediated Currents Are Modulated by Substrate Mechanics. ACS Nano. 13(11): 13545–59.

MR Servin-Vences, M Moroni, GR Lewin, K Poole (2017) Direct measurement of TRPV4 and PIEZO1 activity reveals multiple mechanotransduction pathways in chondrocytes. eLife. 6: e21074.

C. Wetzel, S. Pifferi, C. Picci, C. Gök, D. Hoffmann, K.K. Bali, A. Lampe, L. Lapatsina, R. Fleischer, E.S. Smith, V. Bégay, M. Moroni, L. Estebanez, J. Kühnemund, J. Walcher, E. Specker, M. Neuenschwander, J.P. von Kries, V. Haucke, R. Kuner, J.F.A. Poulet, J. Schmoranzer, K. Poole, G.R. Lewin (2017) Small-molecule inhibition of STOML3 oligomerization reverses pathological mechanical hypersensitivity. Nat. Neurosci. 20: 209–18.

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More Information

On Biophysical Society TV:

Kate talks about mechanically activated ion channels – like PIEZO1, TRPV4, ELKIN1 and TREK-1 – that allow our cells to sense their surroundings in different ways.

Projects

Mechanoelectrical transduction at the membrane-matrix interface

We have developed a sensitive technique using microfabricated surfaces (arrays of flexible cylinders) by which we can apply very fine physical stimuli to cells, directly at the cell-matrix interface. Our earlier work using this technique has allowed us to identify accessory molecules that can tune the sensitivity of mechanoelectrical transduction in distinct subsets of cells. We are currently using such arrays to understand how the membrane environment at cell-matrix contact points can affect the sensitivity of mechanically-gated ion channels. This work involves, not only measuring mechanically-gated ion channel activity, but imaging of the different molecular components that assemble to form force-sensing platforms.

Mechanoelectrical transduction in chondrocytes

The cartilage that lines our joints is comprised solely of extracellular matrix molecules and specialised cells known as chondrocytes. This tissue is not innervated and does not contain any blood vessels, meaning that the chondrocytes alone are responsible for sensing changes in mechanical loading and adapting the production of the extracellular matrix in order to maintain integrity of the cartilage. We are working to identify how channels, extracellular matrix molecules and scaffolding proteins form force-sensing platforms in these cells.

How does mechanoelectrical transduction regulate melanoma metastasis?

Metastasis of melanoma cells away from the primary tumour site carries a very poor patient prognosis, with median survival rates of less than 5 years. We are addressing the question of how melanoma metastasis is effected by mechanically-gated ion channel activity and working to identify the molecules involved. In addition to making sensitive molecular-scale measurements of cellular mechanosensitivity using our pillar arrays we are also using atomic force microscopy and super-resolution imaging techniques to image how the individual components of the force-transduction machinery are arrayed within the cell-matrix interface. We seek to identify ways to manipulate mechanoelectrical transduction in melanoma cells with the aim of blocking metastasis.