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Developing Automated Cell and Exosome Counters for Parkinson’s Disease


Department of Chemistry

About the Project

We current live in a time where the world population is aging, leading to a surge in aged related illness. Neurodegenerative diseases are largely linked to aging, being progressive and for the most part are mostly without cure and only limited treatment options. Parkinson’s disease is the second most prevalent neurodegenerative disease worldwide, with a good level of understanding of the pathology already known, yet how the disease initiates and progresses remains a challenge. Parkinson’s is characterised by a loss of movement control including resting tremors, muscular rigidity, bradykinesia, and general postural instability, resulting from a degeneration of dopamine signalling cells within a central part of the brain. Over the last decade advances have been made in better understanding of the disease, with some links to misfolded α-synuclein proteins known to lead to Lewy bodies and cause cellular dysfunction. There is also well known involvement of microRNAs in Parkinson’s pathogenesis. Being able to diagnose disease at an early stage enables planning and active monitoring to support these patients.

Extracellular vesicular bodies such as microvesicles (MVs) and exosomes are currently under intense investigation. This is due to the wide role they appear to play, at a fundamental level, in many biological processes, both physiological and pathological. MVs originate through at least three mechanisms: (a) breakdown of dying cells into apoptotic bodies; (b) blebbing of the cellular plasma membrane (ectosomes); and (c) the endosomal processing and emission of plasma membrane material in the form of exosomes. Their cellular origin, structure, function and characterization has been extensively reviewed, though still the subject of much debate. The previous lack of suitable methods for their detection, analysis, and phenotyping is proving to be a significant limitation in these studies. Recent research has demonstrated that neuronal-derived MVs isolated from peripheral blood may be useful in the evaluation of neurological diseases such as Parkinson’s disease.

The limitation of current analytical techniques is confounded by the variation in protocols for the purification, isolation and storage of MVs. This project will provide a new technology for the characterisation of MVs direct from cell culture with no sample preparation. With an ability to monitor in real-time the production of MVs within our model “brain-on-a-chip” device. The technology can also isolate individual MVs from the system for further genomic and proteomic studies, This will allow researchers to understand/ follow and characterise the disease in unprecedented detail.

Supervised by Dr Mark Platt and Dr Paul Roach at Loughborough University who bring expertise in 3D printed nanopore sensors for screening biological and inorganic materials within samples, and microfluidic model systems of in vitro brain circuitry designed to accurately reproduce part of the complex circuitry involved in neurodegenerative diseases.

The project will develop a current ‘brain-on-a-chip’ technology to integrate sensors with rapid data extraction/ analysis for the investigation of neurologically derived MV’s. These sensors have the resolution of a single exosome, capable of screening large volumes of liquid for a single or billions of cellular particles. The researchers will have access to our manufacturing facilities, sensors, laboratories and integrated into a vibrant research group researching neurodegenerative diseases. The project will develop, manufacture and test a resistive pulse sensor combined with embedded optical sensors. The outputs from the sensors will be analysed using a range of open access and bespoke statistical software. Data from genomic and proteomic analyses of the extracted MVs will be integrated into the biological model.

Applicants should have a background in chemical and biological sciences, with preference given to applicants with experience and competence in analytical and biophysical analysis. Support and training will be given in all aspects of the project, including photolithography, cell culture, microfluidics design and fabrication and data analysis.

Entry requirements

At least 2:1 (or equivalent) in undergraduate chemistry, biosciences or related discipline.

Loughborough University

Loughborough University is a top-ten rated university in England for research intensity (REF2014). In choosing Loughborough for your research, you will work alongside academics who are leaders in their field. You will benefit from comprehensive support and guidance from our Doctoral College, including tailored careers advice, to help you succeed in your research and future career.

Find out more: http://www.lboro.ac.uk/study/postgraduate/supporting-you/research/

How to apply

Please apply online at https://www.lboro.ac.uk/study/postgraduate/apply/research-applications/ and include reference CM/MP-Un2/2020

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