My research is in theoretical biological physics. This uses approaches from theoretical physics to study biological and biologically inspired systems. In my group we work in collaboration with other scientists from a range of disciplines including biology and medicine. This page outlines some of the problems we are interested in. Please see my
publications for more details.
"Active matter" is material that is out of equilibrium due to its
constitutive components having an internal source of energy that drives the system out of equilibrium. From a physics perspective active matter is a novel type of material that displays rich and interesting behaviours. Active gel theory uses equations developed for viscoelastic gels or liquid crystals and adds terms to describe the "active" out-of-equilibrium nature of materials such as those found in living systems and synthetic active materials.
Active matter theory can be used to model the cytoskeleton of living cells. The cytoskeleton is a biopolymer network made of filamentous proteins such as actin and microtubules shown in read and green in the picture below.
We are particularly interested in actomyosin cytoskeleton made up of actin filaments and myosin molecular motors. By consuming chemical fuel (ATP) the actin filaments grow (polymerise) and the molecular motors can walk along the filaments exerting stress on the actin filaments. The overall effect of the stress exerted by myosin on actin is contraction.
The dynamics of the cytoskeleton drive cell deformation and movement. Using active matter theory to model the cytoskeleton, I seek to better understand the mechanics of cell migration. How do the active properties of the cytoskeleton biological gel enable cells to move independently in a way that non-living gels like hair gel don't?
We are particularly interested in cell motility in confinement. Cells sometimes have to squeeze though small gaps, for example immune cells chasing bacteria or metastatic cancer cells exiting a tumour and moving to form a secondary tumour elsewhere. We develop theoretical models of cell migration in confinement in collaboration with experimentalists in Paris (primarily Matthieu Piel's lab).
For example some years ago we developed an initial simple model for a mechanism for cell motility in confinement which works in a similar way to a rock climber using a technique called "chimneying". The climber pushes against two opposing rock faces in order to gain the friction needed to climb. In a similar way the cell in our mechanism pushes against the confining walls to create the friction needed to move.
The cell nucleus contains the DNA (shown in blue in the image above). When cells squeeze through particularly small gaps the nucleus has to change shape to get through. We are interested in this and other scenarios when the nucleus is deformed. We model the nucleus as an elastic object and calculate the forces required to deform it. Some of the questions we consider are: How does the cell generate the forces needed to push/pull the nucleus? What is the physical role of the nucleus in cell migration? How does the cytoskeleton active gel interact with the nucleus? This work is funded by EPSRC and we are currently collaborating with Matthieu Piel's lab and Denis Wirtz lab.
Metastatic cancer cells
We are interested in using what we have learnt about cell migration in confined environments and the role of the nucleus to better understand cancer metastasis. We are currently focusing on breast cancer bone metastases. We are working with Nicola Brown, Jamie Hobbs, Ashley Cadby, and Ingunn Holen on a cancer research UK funded project.
Endocytosis and phagocytosis are processes in which biological cells take in particles (e.g. molecules or microbes) by engulfing them with membrane. The membrane deforms to engulf the particle and then pinches off into a vesicle inside
the cell. We are interested in the role of actin and other biopolymers in this process. We are currently collaborating with Kathryn Ayscough and Simon Johnston.
The theoretical techniques we use can also be applied to multicellular systems such as tissues. We are currently working with Andrew Fleming and Nick Monk on the dynamics of plant leaf growth.
Single molecule level
My PhD was on the internal dynamics of single protein molecules. I am still interested in questions related to this. How is information transmitted from one binding site to another across a protein? What are the relative roles of changes in average conformation and vibrational modes? How is this relevant to protein signalling?