Cooperative, non-specific binding and aggregation in protein/RNA interactions: Beyond stoichiometry, specificity, and discrete binding sites

Interactions between biomolecules are typically considered to be both specific and stoichiometric. Even in cases of multiple binding sites, cooperative binding models have been successful in reproducing the sigmoidal binding curves seen in experiment (e.g., hemoglobin). However, many important binding phenomena (e.g. specific but sequence-independent interactions between proteins and biological polymers) are not well described by classical cooperative binding models. This failure becomes prominent when the binding site is not localized but spread over a wider surface of the biomolecules, such the surface of a double-stranded nucleic acid. Such interactions are beyond the scope of classical binding models.

A new language is therefore necessary to describe such weak, non-specific binding. Our strategy is to combine theory and experiments. For theory we appeal to the fundamental principles of statistical thermodynamics that are used to rationalize solvation phenomena in solution chemistry and formulation science. We will exploit structural, thermodynamic and hydrodynamic approaches to provide an experimental description of binding. Supervised by experts in theory and experiment, the project aims to establish a molecular-based approach to describe weak, non-specific interactions between proteins, and proteins and nucleic acids, and to furnish a novel method to extract such information from experimental data.

Applications from candidates with a strong background in physical chemistry or soft matter physics are encouraged. Willingness to learn about biomolecules and their behaviours, and to handle diverse experimental techniques will be indispensable.

This prestigious BBSRC funded Doctoral Training Partnership (DTP) brings together the very best molecular, chemical and cellular bioscience research across the White Rose Consortium of Universities (Leeds, Sheffield and York), which maps on to the research themes of the BBSRC. Students will benefit from a regional PhD training programme that has interdisciplinary collaboration at its core. The aim is to enable students to develop a range of research skills in biological and biochemical areas as well as equip them with core mathematical, data analysis and generic professional skills that are necessary for bioscience research in the coming decades. At York, the White Rose Partnership brings together researchers from the Departments of Biology and Chemistry. https://www.york.ac.uk/biology/postgraduate/dtpbbsrc/

Additionally, all Chemistry research students have access to our innovative Doctoral Training in Chemistry (iDTC): cohort-based training to support the development of scientific, transferable and employability skills. https://www.york.ac.uk/chemistry/postgraduate/idtc/

Panel interviews will take place at the University of York on 6 February 2019.

The Department of Chemistry holds an Athena SWAN Gold Award and is committed to supporting equality and diversity for all staff and students. The Department strives to provide a working environment which allows all staff and students to contribute fully, to flourish, and to excel: https://www.york.ac.uk/chemistry/ed/

This PhD will formally start on 1 October 2019. Induction activities will start on 30 September.