EPSRC DTP Studentship – Nucleic acid – polymer hybrids: Fundamental understanding of stabilization of aptamers within a polymer matrix for sensing, diagnostics and therapeutics

Details

Molecular recognition – the interaction between two entities at the molecular scale – is vital to nearly all biological processes and scientists have harnessed this for numerous applications. In many cases antibodies and enzymes are used to great effect but these biological based materials have inherent issues including immunogenicity and environmental stability, limiting wider functionality.

Molecular imprinting involves making a binding pocket inside a polymer which is chemically and shape specific for the target compound. These “smart plastics” offer robustness compared to biological molecular recognition elements such as antibodies and enzymes. They also can work in extreme environmental conditions. However, they sometimes lack the necessary specificity/affinity.

Aptamers are small pieces of DNA/RNA that can selectively target proteins and/or small molecules and bind to them with high specificity and affinity. They are not toxic and are attractive alternatives to antibodies. They have been used primarily in research due to their susceptibility to enzymatic and chemical degradation, though this is slowly changing, and they are becoming commercially relevant.

The Turner Group has recently developed hybrid materials that create a “best-of-both-worlds” approach incorporating aptamers into molecularly imprinted polymers (MIPs) making aptaMIPs. In simple terms, the aptamer structure is modified to allow it to be directly incorporated into a polymer, so it will hold its shape while being protected from environmental conditions. Novel, high affinity and stable materials were created, with the capability to match biological materials in terms of affinity and selectivity. https://doi.org/10.1039/D1PY00607J & https://doi.org/10.1002/gch2.202200215

While the principle of these hybrids has been demonstrated, our understanding of how the process affects the structure and stability of both components (nucleic acid sequence and polymer) is not understood. This project will explore the fundamental physicochemical properties of these with the key aim of improving the capabilities of this class of synthetic molecular recognition material making them more attractive for commercial and clinical use.

Working alongside the Craggs group – specialists in the development and application of single- molecule fluorescence techniques and their use looking at molecular structure and dynamics (https://doi.org/10.1038/s41592-023-01807-0 & https://doi.org/10.1016/j.bpr.2021.100013)– we will look at how the nucleic acid sequences respond to the polymerisation process, with a particular focus of stability and structural changes.

This project will use a wide range of analytical techniques including, but not limited to, Differential Scanning Calorimetry, Isothermal Calorimetry, Circular Dichroism, single-molecule Forster Resonance Energy Transfer, Nuclear Magnetic Resonance, Surface Plasmon Resonance and Thermal Gravimetry; alongside synthetic techniques (polymer and nucleic acid) to explore these materials.

We will focus our efforts on producing aptaMIPs for clinically relevant systems: firstly, on aptamers that recognise prion proteins; and secondly on an existing known therapeutic aptamer for macular degeneration. These will offer impact for this fundamental study.

This project will suit a candidate with a background in Chemistry, Biochemistry, Pharmacology or Molecular Biology, with an interest in molecular recognition, polymer chemistry, molecular structure or analytical science.

The award will fund the full (UK or Overseas) tuition fee and UKRI stipend (currently £18,622 per annum) for 3.5 years, as well as a research grant to support costs associated with the project.

Interested candidates are strongly encouraged to contact either Professor Nick Turner ( n . w . turner @ sheffield . ac . uk ) or Dr Tim Craggs ( t . craggs @ sheffield . ac . uk ) to discuss your interest in, and suitability for, the project prior to submitting your application.

Interested candidates are strongly encouraged to contact the project supervisors to discuss your interest in and suitability for the project prior to submitting your application. 

Please refer to the EPSRC DTP webpage for detailed information about the EPSRC DTP and how to apply.

Project ID: CHM-02-Turner