The development of new techniques for better understanding the behaviour and stability of DNA structures under different environmental conditions is of great importance, as it is likely that these structures can provide a therapeutic target for the treatment of cancer.
It has been shown that biomolecules in an aqueous solution can be studied using terahertz spectroscopy due to changes in the vibrational modes of the surrounding water molecules. This leads to an increase in their absorbance in the terahertz (THz) frequency domain, related to the hydration shell of water molecules surrounding the molecule. We have recently used terahertz spectroscopy to probe the hydration shell of a G-quadruplex forming sequence of DNA. The results showed that the absorbance in the terahertz region is different depending on whether the DNA sequence is folded into a G-quadruplex or not, highlighting the fact that this technique is suitable to study DNA conformation. The study of well-defined DNA sequences using terahertz spectroscopy is very limited, and our current work represents a clear ability to enhance this area of interesting research. The beauty of terahertz spectroscopy is that it provides a label-free, non-destructive technique to probe DNA conformation in solution.
In this project, the student will concentrate on the development of spectroscopic instrumentation and techniques to characterise the terahertz response of nucleic acids in solution. Initially, the student will focus on the design of a new thermally regulated flow cell and integrate it with the existing terahertz spectrometer optics. Data analysis software will be developed for the reliable extraction of the terahertz absorption coefficient and refractive index of the sample solution within the cell, taking into account multiple reflection and beam diffraction effects. Working closely with the Department of Pharmacy, the student will conduct terahertz spectroscopy experiments on DNA samples to characterise the terahertz behaviour of a range of DNA systems for the first time. In addition, they will explore the potential of increasing the sensitivity of the technique so that much smaller quantities of DNA can be measured by exploiting recent developments in terahertz molecular sensing with plasmonic nano-slot resonators, for which an increase of more than three orders of magnitude in the absorption cross-section of molecules has been demonstrated. A novel nano-slot array will be designed and developed for incorporation within the flow cell to dramatically increase the spectroscopic sensitivity to nucleic acid systems.
The understanding gained through this project of the structure and function of DNA duplexes, triplexes and quadruplexes is expected to have a significant impact on the design of suitably targeted drugs for the treatment of cancer, with considerable health benefits for the general public.
School of Systems Engineering, University of Reading:
The University of Reading is one of the UK’s 20 most research-intensive universities and among the top 200 universities in the world. Achievements include the Queen’s Award for Export Achievement (1989) and the Queen’s Anniversary Prize for Higher Education (1998, 2006 and 2009). This project will take place in the School of Systems Engineering (SSE), which has a strong reputation for its innovative research in computer science, cybernetics, and electronic engineering.
Applicants should have a bachelors (at least 2.1 or equivalent) or masters degree in Physics, Systems Engineering, Optics, Cybernetics or a strongly related discipline. Strong experimental skills are preferable. Experience in Matlab is desirable.
How to apply:
(1) Submit an application for a PhD in Cybernetics using the link below.
(2) After submitting your application you will receive an email to confirm receipt; email should be forwarded along with a covering letter and full CV to Dr John Bowen ([email protected]
(3) In the online application system, there is a section for “Research proposal” and a box that says “If you have already been in contact with a potential supervisor, please tell us who” – in this box, please enter “Dr. John Bowen”.
Dr. John Bowen, tel: 0118 9316702, email: [email protected]