Development of novel approaches to regulate stem cell differentiation

Lead Research Organisation: University of York
Department Name: Biology

Abstract

Glycans are carbohydrate polymers which, with proteins, DNA and RNA, are one of the four biopolymers essential for life. Yet our understanding of glycan functions remains rudimentary compared with that of proteins and nucleotides. This is a significant drawback given the well documented importance of glycans in mammalian development, pathology, and longevity. Glycans are commonly attached to proteins or lipids and processed by a large cohort of glycosylation enzymes to form elaborate branched polymer chains. Defects in glycan processing can lead to a number of different diseases, classed as congenital glycosylation disorders (CDGs). Yet known individual glycan functions, such as the function of sialic acid and fucose containing glycans in facilitating leukocytes to leave the circulation at the site of inflammation, is rare.
This PhD project is designed to combine glycobiological methods with the use of cell biological model systems to investigate the functions of different glycans and how they modulate the effects of the proteins they are attached to. As models we will use the differentiation of mesenchymal stem cells (MSCs) into bone (osteogenesis) and fat (adipogenesis), as well as the functionality of the differentiated progeny (e.g. insulin stimulated behaviours). Glycosylation will be modulated using pharmacological agents targeting the processing machinery, as well as gene editing to modify both the expression levels and the sorting of glycosylation enzymes within the cell. The student will be part of a vibrant cell biology community and will be trained in modern cell culture (cell differentiation, CRISPR/Cas gene editing), imaging (confocal, FACS) and glycobiology (mass spectrometric glycan profiling) as well as routine molecular biology and biochemistry methods.
Wilson, KM, JE Thomas-Oates, P Genever, D Ungar (2016) Glycan profiling shows unvaried N-glycomes in MSC clones with distinct differentiation potentials. Front. Cell Dev. Biol., 4:52

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
BB/M011151/1 30/09/2015 29/09/2023
1949513 Studentship BB/M011151/1 30/09/2017 29/09/2021 Sian Rebecca Gregory