Hormone recognition, binding and selectivity
The auxin receptor TIR1 and the related AFBs are expressed from insect cells and binding is explored in terms of kinetics (surface plasmon resonance, Biacore), thermodynamics (isothermal titration calorimetry, ITC) and structure. This project is joint with Dr Stefan Kepinski (University of Leeds, UK). It is known that auxin completes a nascent substrate binding pocket as it binds to TIR1. The substrates are the Aux/IAA transcriptional regulators which, on binding, become ubiquitinated through the ubiquitin E3 ligase activity of TIR1. We are exploring how selectivity is conferred for different auxins and different Aux/IAAs, and how these two variables affect each other. We are building pharmacophoric maps of auxin receptors in order to inform rational design and selection of novel auxins and anti-auxins.
Auxin transport proteins
We are starting to examin auxin transport proteins with the same degree of molecular precision. We recently published a pharmacophoric map of the auxin uptake carrier AUX1, and a model of PIN2.
Biosensors, like receptor proteins, need to recognise analytes with appropriate sensitivity and selectivity. The group is developing hormone sensor domains in order to generate experimental plant hormone biosensors. We are working with Prof Nick Dale (University of Warwick), a neurobiologist and specialist in the development of purine biosensors, to develop a microelectrode-based biosensor for cytokinins. This work is in collaboration with Prof Ivo Frebort (University of Olomouc).
E-noses in agriculture
Electronic devices for detecting volatiles have developed rapidly and small, portable and highly sensitive deveices are available for a wide range of applications. Communication via volatiles is commonplace in nature and I am interested in applying e-noses as real-time sensors for biological responses for the benefit of agriculture.
PhD Projects available for 2018:
How did selectivity for the one natural auxin IAA evolve? Are there still novel natural auxins to be discovered? From the structural biology of the auxin receptor TIR1 we have learnt a great deal about how auxin is recognised and how it starts the signalling cascades which alter plant development. Work in our lab has also shown how a different member of the auxin receptor family (AFB5) has a different, wider selectivity profile. An important family of auxin herbicides work through AFB5, and AFB5 is also implicated in the control of branching. This project will explore how and why the receptors have come to differ, and whether there might be a novel plant hormone to be discovered.
Structural biology of auxin transport proteins: a project with Dr Alex Cameron (Life Sciences, Warwick). The goal is to express, purify and determine the structure of auxin transport proteins by crystallography. These transporters determine some of the most profound morphogenic events in biology, such as polarity in the embryo, and yet we have no mechanistic understanding of how they work.
How do entropies and energies drive selective binding of an intrinsically-disordered protein? a project wiht Dr del Genio (visiting academic, Warwick). This is a project for someone interested in applying biophysics and mathematics to biology. The goal is to explain selective binding of Aux/IAA proteins to the hormone receptor TIR1. You will combine calculations with laboratory work using purified proteins to test the contributions of key residues in both partners using mutagenesis in order to explain selectivity.