Autophagy in Mesenchymal Stem Cell Fate Determination

Project Overview

Osteoporosis has been widely studied for decades yet ways to reverse bone loss once it has occurred are few and the increasing population age makes this an area of critical research and clinical need. Ageing is associated with a preferential increase in bone marrow fat, something that is also observed in osteoporosis1. Mesenchymal stem cells (MSCs) are the common progenitor cell of adipocytes and bone forming osteoblasts. Studies indicate that ageing decreases the bone marrow MSC pool as well as biased differentiation into adipocytes at the cost of osteoblasts; this alteration in balance is thought to underlie the etiology of osteoporosis.

Autophagy is critical for the proper turnover of organelles such as endoplasmic reticulum and mitochondria and its dysregulation is incriminated in various metabolic disorders2. Autophagy has been identified as an important determinant of bone homeostasis and a decline in autophagy as a contributor to skeletal aging3. To date the link between MSC fate in the bone marrow and autophagy has not been investigated. It is hypothesised that a down regulation of autophagy with age predisposes MSC fate towards the adipocyte lineage resulting in the bone loss associated with osteoporosis. This project will investigate the role of autophagy in MSC fate with a view to developing new therapeutic approaches for bone loss disorders.

Training 

The Kennedy Institute is a world-renowned research centre housed in a brand new state-of-the-art research facility in Oxford. Full training will be provided in a range of cell and molecular biology techniques as well as in vivo disease models. Students will receive specialist training on state-of-the-art in vivo imaging technologies. A core curriculum of 20 lectures will be taken in the first term of year 1 to provide a solid foundation in musculoskeletal sciences, immunology and data analysis. Students will attend weekly departmental meetings and will be expected to attend seminars within the department and those relevant in the wider University. Subject-specific training will be received through our group's weekly supervision meetings. Students will also attend external scientific conferences where they will be expected to present their research findings.

Relevant Publications

1. Yeung et al J. Magn. Res. Imaging 2005 22(2):279-85 
2. Zhang H et al. Trends Mol Med. 2016 22(8):671-86. 
3. Onal et al JBC 2013 288(24):17432-40.

Scientific Themes

Musculoskeletal Science; immunology; innate immunity and inflammation.

Further information

Prof Nikki Horwood, Kennedy Institute, University of Oxford
nicole.horwood@kennedy.ox.ac.uk