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Mitochondrial dysfunction in ARDS and therapeutic mechanism of mesenchymal stromal cell derived extracelluar vesicles


Project Description

Acute Respiratory Distress Syndrome (ARDS) is a major cause of acute respiratory failure in critically ill patients requiring mechanical ventilation, with no effective treatment and is associated with high mortality and morbidity. Mitochondrial dysfunction and its potential mechanistic role in the evolution of lung diseases have become increasingly recognized as an important and translationally promising research field. Strategies aiming to protect mitochondria from injury or to enhance biogenesis are being actively explored as potential therapeutic opportunities. Mesenchymal Stem Cells (MSC) are a novel potential therapy for this syndrome of acute respiratory failure. Accumulating evidence now suggests that MSCs act primarily through their secretome, key components of which are extracellular vesicles (EVs). MSC-derived EVs are increasingly considered to constitute a compelling alternative to the whole cell therapy. EVs have emerged as important mediators of cell-to-cell communication. These membrane-bound compartments carry multiple different molecules including proteins and different species of RNA as well as whole organelles such as functionally active mitochondria. Dr Krasnodembskaya’s group is funded by MRC to develop MSCs EVs as cell-free innovative stem cell therapy product. To effectively and safely translate EVs into clinical application, there is a need for a better understanding of their mechanisms of action. The first aim of this PhD project is to investigate mechanisms responsible for mitochondrial dysfunction in ARDS and its impact to ARDS pathophysiology using clinically relevant in vitro models. Second aim of the project is investigate therapeutic potential of mesenchymal stromal cell derived extracellular vesicles to alleviate consequences of mitochondrial dysfunction.

The student will apply a number of techniques, including cutting edge human lung tissue models, cell culture, immunohistochemistry, confocal microscopy. The project is suitable for a self-motivated, hard-working student with strong interests in cell based therapies. The outcomes of this research project are expected to be presented at national and international scientific meetings and published in the high impact respiratory journal.

ENTRY REQUIREMENTS

Candidates should have or expect to obtain a 2:1 or higher Honours degree or equivalent in a relevant biomedical or life sciences subject.

English Language

Candidates applying from countries where the first language is not English should produce evidence of their competence through a qualification such as IELTS or TOEFL score.

The minimum recommended score for the School of Medicine, Dentistry and Biomedical Science is:
• IELTS score of 6.0 with not less than 5.5 in each of the four component elements of listening, reading, speaking and writing taken within the last 2 years;
• TOEFL score of 80+ (internet basted test), taken within the last 2 years, with minimum component scores of; Listening 17, Reading 18, Speaking 20, Writing 17);
• A valid Certificate of Proficiency in English grade A or B;
• A valid Certificate of Advanced English grade A; or
• A first or upper second class honours degree from a university based in the UK, Republic of Ireland or other suitably quality assured location in a country deemed by the UK Border Agency to be majority English speaking.

For a list of English Language qualifications also accepted by the School and University please see the following link:
http://www.qub.ac.uk/International/International-students/Applying/English-language-requirements/#English

INTO Queen’s English Language Courses offers both pre-sessional and in-sessional courses in English for academic purposes and study skills. Courses vary in length and full information can be obtained at: https://www.qub.ac.uk/International/International-students/Applying/University-Preparation-Courses/INTOEnglishlanguagecoursesatQueens/

Funding Notes

*FUNDING CONFIRMED – Department for the Economy (DfE) Award*

Eligibility for both fees (£4,327 for 2019/20, 2020/21 TBC) and maintenance (£15,009 for 2019/20, 2020/21 TBC) depends on the applicants being either an ordinary UK resident or those EU residents who have lived permanently in the UK for the 3 years immediately preceding the start of the studentship.

Non UK residents who hold EU residency may also apply but if successful may receive fees only.

For further details re eligibility criteria (including academic, citizenship and residency criteria) please click on the following link: View Website

References

Please visit the School of Medicine, Dentistry and Biomedical Sciences, Centre for Experimental Medicine, website for further details about the Centre:

http://www.qub.ac.uk/research-centres/CEM/

When applying, please choose 'MEDICINE' as your subject area/School.

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