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EastBio Fluorescence lifetime imaging of proteins in the brain

  • Full or part time
    Dr Matthew Horrocks
  • Application Deadline
    Sunday, January 05, 2020
  • Competition Funded PhD Project (European/UK Students Only)
    Competition Funded PhD Project (European/UK Students Only)

Project Description

As we age, our proteins can misfold and clump together forming insoluble deposits. This process is particularly common in the brain, and can lead to neurodegenerative disorders including Alzheimer’s and Parkinson’s disease. We have previously used advanced super-resolution microscopy techniques to understand this process in the test tube and in cells1. We now wish to further our knowledge by looking at the end results of this in post-mortem brain slices.

Fluorescence microscopy provides the means to specifically image proteins within complex environments, such as the brain. However, this usually relies on covalently attaching an organic fluorophore to the protein, which is not possible within tissue. To circumvent this, we have developed a range of fluorescent peptides that are able to bind specifically to their target protein2. Rather than relying on only the intensity, the fluorescence lifetime of the probe can provide information about its local environment. We will measure this using newly-developed spectrally resolved fluorescence lifetime imaging (FLIM) technology3, allowing the aggregation state of the protein to be determined. The method will first be optimised on purified protein, before being used with human post-mortem tissue from the brain bank.

Training: the supervisors of this project will combine their expertise in peptide design and synthesis, neuroscience and microscopy techniques. The training will be achieved through application of the research techniques within the supervisors’ and collaborators’ laboratories. Skills that will be developed include organic synthesis of peptides, fluorescence characterisation of probes, advanced microscopy (single-molecule and fluorescence lifetime), data analysis and coding. The student will be encouraged to participate in training workshops, to present in various multi-group meetings at the university, and to participate in public engagement activities. The supervisors will ensure that the student also has the opportunity to attend and present at international conferences.

Application Process:
To apply for an EASTBIO PhD studentship, follow the instructions below:
1) Check FindaPhD for our available projects and contact Dr Mathew Horrocks before you apply.

2) After you have discussed the projects of interest to you with the project supervisors, download and complete our Equality, Diversity and Inclusion survey and then fill in the EASTBIO Application Form and submit to each of your proposed projects as per the instructions in the project adverts.

3) Send the EASTBIO Reference Form to your two academic/professional referees, and ask them to submit as specified on the project adverts.

4) If you are nominated by the supervisor(s) of the EASTBIO PhD project you wish to apply for, they will provide a Supervisor Support Statement.

5) We anticipate that our first set of interviews will be in the week commencing 10th February 2020 with awards made the following week.

If you have further queries about the application/recruitment process please email EastBio.

Please ask your referees to submit your references directly to Dr Mathew Horrocks

Equality and Diversity Clause – this should be included in every advert
The School of Chemistry holds a Silver Athena SWAN award in recognition of our commitment to advance gender equality in higher education. The University is a member of the Race Equality Charter and is a Stonewall Scotland Diversity Champion, actively promoting LGBT equality. The University has a range of initiatives to support a family friendly working environment. See our University Initiatives website for further information. University Initiatives website: https://www.ed.ac.uk/equality-diversity/help-advice/family-friendly

Funding Notes

This 48 month fully-funded PhD position is supported through the BBSRC EastBio Doctoral Training Partnership. Applicants must hold a first or upper second class UK honours degree or equivalent and must meet RCUK residency requirements. More information can be found here: View Website

References

1. Whiten, D. R. et al. Nanoscopic Characterisation of Individual Endogenous Protein Aggregates in Human Neuronal Cells. ChemBioChem 19, (2018).
2. Mendive-Tapia, L. et al. Spacer-free BODIPY fluorogens in antimicrobial peptides for direct imaging of fungal infection in human tissue. Nat. Commun. 7, 10940 (2016).
3. Ahmet T. Erdogan. et al. A CMOS SPAD Line Sensor With Per-Pixel Histogramming TDC for Time-Resolved Multispectral Imaging. J. Solid-State Circuits. 54. 1705-1719

How good is research at University of Edinburgh in Chemistry?
(joint submission with University of St Andrews)

FTE Category A staff submitted: 43.30

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

Click here to see the results for all UK universities

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