(MRC CASE) Video rate imaging of dynamic processes in living cells, at industrial scale, but on an academic budget

The Daniels lab (Cardiovascular Sciences, FMHB) develops new ways to see aspects of common inherited cardiac conditions using a combination of fluorescent protein engineering, and stem cell biology with conventional microscopy infrastructure and manual image analysis. The other academic partners have established interests in complimentary areas of cardiovascular disease which have historically included a component of live cell 2D imaging. These experimental platforms have potential to be converted into phenotype based screening assays which can enable drug or genetic discoveries. The limiting factor is the cost and scale that current experimental work can be performed at.

CytoSMART Technologies BV (https://www.cytosmart.com/) are an innovative Dutch SME based in the tech corridor in Eindhoven, NL, that combines innovative product design, and automated image analysis with cloud based computing to advance in-incubator live cell imaging. The principal applicants have worked together since 2015, outputs from which included automated image analysis for contraction/relaxation kinetics for iPS-cardiomyocytes, and an inexpensive adaptation of the CytoSMART lux to enable low cost prolonged live cell imaging inside widely used low cost hypoxia chambers.

A major limitation of the current live cell imaging strategies at the scales used by the Daniels group and others is throughput. A one:one relationship exists between the experimenter and the dish which is then followed by time consuming manual analysis. This means that we can test only a handful of drugs/doses (when drug discovery needs us to test thousands of compounds across 5 log scales of concentration) or mutations (>1000 are described for the disease of interest). The CytoSMART OMNI device delivers multi-well in-incubator imaging capabilities on an academic budget using a scanning CMOS detector and mobile lighting gantry. This project seeks to develop and apply the OMNI platform for use with fluorescent probes of cardiac contraction, or calcium, and with bioluminescent probes for insulin release. In essence we want to adapt the proven black and white imaging capabilities of the OMNI platform to see the various colours we, and others, have developed of disease relevant biology. The academic partner will benefit from the first mover capabilities to work at industrial scale, but at academic cost. The student will benefit from the parallel focus on cell biology and hardware development. The post would be suited to students with an engineering background wishing to utilize biological systems, or biologists wanting to develop core skills in software or hardware development.

https://www.cytosmart.com/
https://www.research.manchester.ac.uk/portal/neil.hanley.html
https://www.research.manchester.ac.uk/portal/holly.shiels.html
https://www.research.manchester.ac.uk/portal/adam.greenstein.html
(Daniels lab page pending, previously https://www.rdm.ox.ac.uk/people/matthew-daniels)

Entry Requirements:
Applicants must have obtained, or be about to obtain, at least an upper second class honours degree (or equivalent) in a relevant subject.

UK applicants interested in this project should make direct contact with the Primary Supervisor to arrange to discuss the project further as soon as possible. International applicants (including EU nationals) must ensure they meet the academic eligibility criteria (including English Language) as outlined before contacting potential supervisors to express an interest in their project. Eligibility can be checked via the University Country Specific information page (https://www.manchester.ac.uk/study/international/country-specific-information/).

If your country is not listed you must contact the Doctoral Academy Admissions Team providing a detailed CV (to include academic qualifications – stating degree classification(s) and dates awarded) and relevant transcripts.

Following the review of your qualifications and with support from potential supervisor(s), you will be informed whether you can submit a formal online application.

To be considered for this project you MUST submit a formal online application form - full details on how to apply can be found on the MRC Doctoral Training Partnership (DTP) website www.manchester.ac.uk/mrcdtpstudentships

Equality, diversity and inclusion is fundamental to the success of The University of Manchester, and is at the heart of all of our activities. The full Equality, diversity and inclusion statement can be found on the website https://www.bmh.manchester.ac.uk/study/research/apply/equality-diversity-inclusion/