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 biomolecule, 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 these weak, non-specific but functionally important interactions. Our strategy is to combine theory and experiment. 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 behaviour, and to handle diverse experimental techniques will be indispensable.

All research students follow our innovative Doctoral Training in Chemistry (iDTC): cohort-based training to support the development of scientific, transferable and employability skills. All research students take the core training package which provides both a grounding in the skills required for their research, and transferable skills to enhance employability opportunities following graduation. Core training is progressive and takes place at appropriate points throughout a student’s higher degree programme, with the majority of training taking place in Year 1. In conjunction with the Core training, students, in consultation with their supervisor(s), select training related to the area of their research.

Theory development; analysis and interpretation of data; Structural biology (NMR and spectroscopy); Biochemical thermodynamics (calorimetry and other solution biophysical techniques).

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. Chemistry at York was the first academic department in the UK to receive the Athena SWAN Gold award, first attained in 2007 and then renewed in October 2010 and in April 2015.