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Building bionanohybrid circuits: understanding and applying single protein molecule function


Project Description

Merging ideas and principles from biology with the physical sciences has proved pivotal in improving our fundamental understanding of nature and the generation of new technologies that impact on our everyday lives. Your project aims to embrace this principle to look at how individual protein molecules function and how these emergent properties can be used in new nanoscale applications.

It has recently emerged that proteins are inherently conductive and biomolecular events related to their function can modulate conductance. Your project will utilise this exciting new concept to develop and apply solution-compatible integrated bioelectronic devices. Building on recent work by the supervisory team you will generate single protein molecule junctions between carbon nanotubes (CNTs) and measure conductance across the protein junction. Dynamic changes in the protein structure and function will alter conductance characteristics and output signal in real time. This novel conductance-based approach will allow fundamental investigations of protein function with single molecule resolution and will in the longer term facilitate applications in biomolecular electronics and biosensing. Crucially, you will be able to control the orientation and thus conductance pathway through the protein by incorporating new chemical coupling handles at designed amino acid residue positions that will define the protein bridging configuration. This will allow unprecedented access to protein function at the single molecule level and provide new insights in the underlying processes by which proteins conduct.

You will focus on two protein systems. The first is fluorescent proteins which will allow you to optically gate conductance across the junction so generating light-gated bio-transistors. The second relates to one of the grand challenges in healthcare: antimicrobial resistance (AMR). -lactamase (BL) enzymes that break down the most important class of antibiotics, the -lactams (e.g. ampicillin) will act as the molecular bridges and electrical signals will be mapped onto events in the catalytic process.

The project lies at the interface between nanoscience and synthetic biology, merging ideas from physics, chemistry and the life sciences so immersing you within an inter-disciplinary environment, a facet currently in demand in both academic and commercials sectors. The nature of the project means you be trained in a wide variety of techniques including protein design, genetic manipulation, non-natural amino acids incorporation, protein chemistry, single molecule imaging, nano-scale fabrication and quantitative data analysis.

You will also benefit from a supportive and experienced supervisory team that have established research groups with the required expertise and infrastructure. The project team has a unique combination of expertise, with a strong background in engineering proteins for nanoscale applications (Macdonald/Jones), single molecule imaging (Macdonald/Castell) and nanoscale fabrication and measurement of bionanohybrids (Jones and Matteo Palma, Queen Mary University London). Students from these labs have successfully published their work in international journals and many have taken up positions in highly regarded academic institutions or technology companies.

EPSRC funded DTP PhD Studentship within the Interdisciplinary Doctoral Training Hub “Physics of Life”
The Hub is designed as a cross-disciplinary PhD research and training programme at the physics/life science interface. Students will benefit from joint supervision across the Colleges of Physical Sciences and Life Sciences at Cardiff University. Each project commences with two 3-months stages in the labs of the joint supervisors. The Hub will offer cohort development opportunities through joint research meetings, a “Physics of Life” summer school in 2022, and a student-led workshop in 2023. Students will be part of a vibrant, interactive community, sharing monthly newsletters and connected via a dedicated portal. Each student will be supported by a mentor. The Physics of Life Doctoral Training Hub aims to equip PhD candidates with multidisciplinary research skills that are highly sought after in academic and industry.

How to Apply:

Applicants should submit an application for postgraduate study via the Cardiff University webpages (https://www.cardiff.ac.uk/study/postgraduate/research/programmes/programme/physics-and-astronomy) including:

• an upload of your CV
• a personal statement/covering letter
• two references
• Current academic transcripts

Applicants should select Doctor of Philosophy, with a start date of October 2020

In the research proposal section of your application, please specify the project title and supervisors of this project and copy the project description in the text box provided. Candidates should hold a good bachelor’s degree (first or upper second-class honours degree) or a MSc degree in Physics or a related subject. Applicants whose first language is not English will be required to demonstrate proficiency in the English language (IELTS 6.5 or equivalent).


Funding Notes

This is a fully-funded studentship which includes fees, stipend and a research and training support grant, for 3.5 years at UKRI rate, for home/EU students.
Self-funded international students are also welcomed to apply.

References

Thomas et al (2020). Site-specific protein photochemical covalent attachment to carbon nanotube side walls and its electronic impact on single molecule function. Bioconjugate Chemistry (10.1021/acs.bioconjchem.9b00719).
Freeley, M.et al. 2017. Site-specific one-to-one click coupling of single proteins to individual carbon nanotubes: a single-molecule approach. Journal of the American Chemical Society 139(49), pp. 17834-17840. (10.1021/jacs.7b07362)

How good is research at Cardiff University in Physics?

FTE Category A staff submitted: 19.50

Research output data provided by the Research Excellence Framework (REF)

Click here to see the results for all UK universities

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