PhD Research Project: Novel strategies to deliver drugs and organelles to the cellular cytoplasm

Impaired function of organelles is an important component of cellular dysfunction and death in a number of diseases. For example, mitochondrial dysfunction is the dominant pathology in mitochondrial encephalopathy lactic acidosis and stroke-like episodes (MELAS) which is characterised by progressive and devastating neurological and systemic symptoms. A number of other conditions such as cerebral ischaemia, trauma, and many neurodegenerative diseases are characterised by impaired mitochondrial function in their pathogenesis.

Similarly, lysosomal and proteosomal dysfunction has been implicated in protein aggregation diseases such as Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, Huntington’s disease, dementia with Lewy bodies, frontotemporal dementia and multi system atrophy. An attractive and novel therapeutic approach for these diseases involves the delivery of healthy organelles to the cellular cytoplasm which may restore the health of diseased cells by providing organelles that could perform or take over the function of the diseased or damaged organelles.

In principle, this seems like an attractive therapeutic approach, but delivery of large cargoes in the micron range presents many challenges. While a huge amount of research has focused on utilising nanotechnology to deliver small molecules and cargoes to the cell, comparatively little work has been done on the cytoplasmic delivery of large cargos like organelles.

Cells do have the ability to take up molecules using a variety of processes including diffusion, active transport, endocytosis (pinocytosis) and phagocytosis. However, little is known about the uptake of large structures like organelles. Recent studies have suggested that cells may have the ability to take up extracellular debris (micron range) and even fragments of mitochondria extruded from nearby cells. These recent findings indicate that cellular uptake of large structures is possible although it appears to occur at low levels in health and disease.

We will explore three novel strategies to deliver organelles in to the cell cytoplasm.

While getting the organelles into the target cell presents challenges, it is not known how the host cell will deal with the new healthy organelles and whether the new organelles will retain function and for how long. This project seeks to answer these questions using mitochondria as the target organelle.

How to apply

Please complete a University Postgraduate Research Application form available here:
http://www.shef.ac.uk/postgraduate/research/apply

Please clearly state the prospective main supervisor in the respective box and select Neurosciences as the department.

Funding Notes

Doctoral Academy Scholarships

The Faculty Scholarships for Medicine, Dentistry & Health cover fees and stipend at Home/EU level. Overseas students may apply but will need to fund the fee differential between Home and Overseas rate from another source.

Chinese Scholarship Award

For eligibility requirements please see the following link https://www.sheffield.ac.uk/postgraduate/research/scholarships/csc
The Chinese Scholarship Award cover fees and stipend including any additional overseas level fees.

 

Eligibility Requirements

Home /EU students must possess a 1st Class Honours or 2:1. Minimum of a merit if MSc has been completed.