Significant recent developments that lay the groundwork for this project include proof of concept testing of real time measurements of DNA and protein molecular dynamics using temperature jump spectroscopy methods to observe biomolecular processes in real time,e.g 4 and demonstration of high throughput 2D-IR screening experiments for DNA-ligand interactions.5 This project will take the next steps in exploiting internationally-leading laser technology for 2D-IR studies of key biological intermolecular interactions (e.g protein-small molecule, DNA-small molecule). In addition to new ways of understanding biomolecular processes in solution, these new directions will make 2D-IR techniques more accessible to potential end users, including the commercial sector.
Strand 1: High throughput 2D-IR spectroscopy of biomolecular complexes: This strand will develop the use of high throughput 2D-IR methods for observing small molecule binding to proteins. This will extend recent work on DNA-binding systems to the spectroscopically more complex and subtle problem of protein-drug binding. In particular, we will target the use of 2D-IR to report on changes in protein dynamics and intramolecular vibrational coupling upon drug binding, linking spectral observables to biological function or physical phenomena such as binding constants. In addition to expanding our 2D-IR capability, this will further studies linking protein molecular dynamics to antibiotic resistance.6
Strand 2: Real time measurements of biomolecular interactions: This strand will develop modified T-jump IR and T-jump 2D-IR spectroscopy-based strategies that allow observation of dynamic non-equilibrium responses of biomolecules to steps in temperature, but extend them to allow combined heating/cooling experiments. These will be used to observe examples of dynamic biomolecular structure change in solution both during the initial perturbation but also upon relaxation, giving new access to the process of location of the binding site by the ligand and so direct observation of mechanisms such as induced fit or conformational selection.
The project will suit students with background in spectroscopy, physical chemistry or biophysics and with an interest in multidisciplinary research. The multidisciplinary nature of the work means that the project would also suit students with a background in molecular biology or data analysis methodologies but with the motivation to learn advanced laser spectroscopy techniques.
1. Hunt, N. T., Transient 2D-IR spectroscopy of inorganic excited states. Dalton Trans 2014, 43, 17578-17589.
2. Adamczyk, K.; Candelaresi, M.; Robb, K.; Gumiero, A.; Walsh, M. A.; Parker, A. W.; Hoskisson, P. A.; Tucker, N. P.; Hunt, N. T., Measuring Protein Dynamics with Ultrafast Two-Dimensional Infrared Spectroscopy. Meas Sci Tech 2012, 23, 062001.
3. Hunt, N. T., Ultrafast 2D-IR Spectroscopy – Applications to Biomolecules. Chem Soc Rev 2009, 38, 1837-1848.
4. Sanstead, P. J.; Stevenson, P.; Tokmakoff, A., Sequence-Dependent Mechanism of DNA Oligonucleotide Dehybridization Resolved through Infrared Spectroscopy. J Am Chem Soc 2016, 138 (36), 11792-11801.
5. Fritzsch, R.; Donaldson, P. M.; Greetham, G. M.; Towrie, M.; Parker, A. W.; Baker, M. J.; Hunt, N. T., Rapid screening of DNA-ligand complexes via 2D-IR spectroscopy and ANOVA-PCA Analytical Chemistry 2018, doi: 10.1021/acs.analchem.7b04727.
6. Shaw, D. J.; Hill, R. E.; Simpson, N.; Husseini, F. S.; Robb, K.; Greetham, G. M.; Towrie, M.; Parker, A. W.; Robinson, D.; Hirst, J. D.; Hoskisson, P. A.; Hunt, N. T., Examining the role of protein structural dynamics in drug resistance in Mycobacterium tuberculosis Chemical Science 2017, 8, 8384-8399.
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. In addition, training in ultrafast spectroscopy methods, sample handling and preparation and data analysis methods will be given as part of the project.
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. This PhD project is available to study full-time or part-time (50%).
Details of 50% Chemistry Teaching Studentship:
Role and Responsibilities:
To assist with undergraduate practical Chemistry teaching for 3 years. This is likely to equate to:
Undergraduate term time:
• 37 hours of demonstrating per year in the undergraduate teaching laboratories. Most of your teaching duties will take place in Autumn and Spring term
• 2.5 hours per year of departmental tours for UCAS visit days in the Autumn Term
Other teaching related duties to enable you to develop your skills, e.g. development of laboratory/Virtual Learning Environment material, assisting with workshops, as well as personal training and development sessions. You will complete a timesheet each term and during the summer vacation and submit them to the Chemistry Graduate Office to record your teaching activities
In common with all graduate students, you will receive training provided by the Chemistry Department and the University’s Research Excellence Training Team (RETT). The Chemistry Department has a Graduate Teaching Assistant (GTA) Training Programme for assisting in laboratory practicals. You will receive additional training specific to developing teaching material online and assessing practical work.
You will have the opportunity to take courses offered by the RETT via the Postgraduates Who Teach programme; e.g. Introduction to Learning and Teaching, Teaching Small Groups, Demonstrating in Science. Further development is possible through engagement with the HEA accredited ‘Preparing Future Academics’ programme.
This training will be complemented by research training integral to your PhD programme. Collectively, experience of research and teaching methods should place you in a strong position for future employment in teaching, academia or other related fields.
Supervision and Mentoring:
Your research will be supervised by your academic supervisor, and you will also be mentored by a second or third year PhD Teaching Student, with overview and input from the Teaching Laboratory Coordinator.
At your Thesis Advisory Panel meetings you will produce a brief one page overview of your teaching activity, and reflect on your skills development in the teaching area. Your Independent Panel Member will take a role in guiding teaching skills development, in consultation with your mentor and the Chair of the Board of Studies.
Chemistry Graduate Office<br>
+44 (0)1904 324544<br>
Eligibility: Studentships are available to any student who is eligible to pay tuition fees at the home rate: https://www.york.ac.uk/study/postgraduate-research/fees/status/