Surrey Group

Previous and current research

The cytoskeleton is responsible for the internal organisation of eukaryotic cells. Microtubules, motor proteins and associated proteins form a mechano-chemical network that determines the dynamic and adaptable nature of intracellular order. But how the collective behaviour of various differently moving motors and competing regulators of microtubule dynamics leads to specific organisations of the cytoskeleton is not understood. How do single molecules move in cells? What role does spatio-temporal control of activities play in the correct functioning of motor/microtubule networks? Can we construct minimal systems in vitro that display complex network dynamics with defined functionalities? And does such a synthetic approach help us to understand what is special about the functioning of mechano-chemical systems distant from thermodynamic equilibrium?

We address these questions using a combination of advanced light microscopy, biochemistry and quantitative cell biology. Our aim is to understand the behaviour of dynamic systems based on measured molecular properties. Therefore, we have studied how single fluorescently-labelled motors behave on single microtubules populated with competing molecules (Telley et al., 2009, Biophys.J.).We have measured the movements of motors in intact mitotic spindles and have investigated how the biophysical properties of an essential mitotic motor are regulated by a kinase in its physiological context. We believe that in vitro reconstitutions of dynamic cytoskeleton behaviour from a minimal set of dynamically interacting proteins is a powerful approach for the dissection of systems behaviour. Microtubule end-tracking and self-organisation of networks consisting of microtubules and different motors (Surrey et al., 2001, Science) are examples where system dynamics can be understood based on biochemical reconstitution combined with quantitative analysis.

Future projects and goals

In the future, we will continue to measure the biophysical properties of motors and microtubules both in their physiological context and in vitro, aiming at connecting single molecule physics with systems behaviour.We will develop tools that will allow us monitor and manipulate the spatio-temporal regulation of protein activities using chemical biology approaches in combination with advanced light microscopy. We will continue to generate more and more complex dynamic systems in vitro and to dissect their functions at a molecular level. Examples are microtubule end-tracking networks, mitotic spindles and cytoskeleton-membrane systems. Our goal is to understand how biological function of protein interaction networks is generated from the coordinated and regulated dynamic interactions of their components. In summary, we are interested in elucidating the design principles underlying intracellular organisation and dynamics using a combination of top-down and bottom-up approaches.