Kate Poole

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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.

About Kate Poole

Dr Kate Poole is a lecturer at UNSW. She received her PhD from the University of Adelaide in 2002 before moving to Germany to undertake postdoctoral studies. She worked in the group of Prof. Daniel Müller at the Max Planck Institute for Molecular Cell Biology and the Technische Universität Dresden, both in Dresden, Germany from 2002-2005 before spending a couple of years working in industry for the Atomic Force Microscopy company, JPK Instruments, AG. Kate returned to research science in 2008 when she joined the laboratory of Prof Gary R. Lewin as a postdoc, at the Max Delbrück Center for Molecular Medicine in Berlin. In 2012 Kate received the Cecile Vogt Fellowship in order to establish her independence, also at the Max Delbrück Center in Berlin, Germany.

Publications

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 (2016) Small-molecule inhibition of STOML3 oligomerization reverses pathological mechanical hypersensitivity. Nat. Neurosci. doi:10.1038/nn.4454.

M. Grandin, M. Meier, J.G. Delcros, D. Nikodemus, R. Reuten, T.R. Patel, D. Goldschneider, G. Orriss, N. Krahn, A. Boussouar, R. Abes, Y. Dean, D. Neves, A. Bernet, S. Depil, F. Schneiders, K. Poole, R. Dante, M. Koch, P. Mehlen, J. Stetefeld. (2016) Structural Decoding of the Netrin-1/UNC5 Interaction and its Therapeutical Implications in Cancers. Cancer Cell 29, 173-85.

K. Poole, R. Herget, L. Lapatsina, HD. Ngo, G.R. Lewin. (2014) Tuning Piezo ion channels to detect molecular-scale movements relevant for fine touch. Nat. Commun. doi: 10.1038/ncomms4520.

L.Y. Chiang, K. Poole, B.E. Oliveira,  N. Duarte, Y.A. Bernal-Sierra, L. Bruckner-Tuderman, M. Koch, J. Hu, G. R. Lewin. (2011) Laminin-332 coordinates mechanotransduction and growth cone bifurcation in sensory neurons. Nat. Neurosci. 14: 993–1000.

S.G. Lechner,S. Markworth, K. Poole, E. St.J. Smith, L. Lapatsina, S. Frahm, M. Suzuki, I. Ibañez-Tallon, F.C. Luft, J. Jordan, G.R. Lewin. (2011) The molecular and cellular identity of peripheral osmoreceptors. Neuron 69: 332-344.

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More Information

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.