Joshua Grieg PhD



King's College London

My research journey began with my undergraduate and master's degrees in Newcastle University, located in the north of England near the Scottish border. Here, my work focussed on understanding the expression of a group of cell adhesion and signalling proteins which are involved in early human brain development, particularly those for which there is an association with autism spectrum disorder (ASD).

From this I developed a keen interest in the role of cell-cell adhesion and how alterations of this perturb cellular function. As such for my PhD research, at the University of Sheffield, I undertook work to elucidate the role of cell surface remodelling, by a process known as endocytosis, and the interaction of mechanical forces during tissue rearrangements. I used a classical model organism: the fruit fly (Drosophila) which undergoes various developmental and morphological changes during its lifecycle, to study these processes. I characterised an interaction network between endocytosis and the mechanical machinery present at the cell surface which balances mechanical force and cell surface remodelling, that enables cell shape changes and ultimately facilitates tissue architecture to be shaped and remodelled.

During my PhD I became more interested in the field of mechanobiology, and the question of how physical forces influences biological behaviours. For my first Post-doc position at University College London (UCL) I studied the pathway which regulates the cellular distribution of the insulin-responsive glucose transporter GLUT4, which is only expressed in skeletal muscle and fat tissue. I discovered and characterised a protein interaction network which regulates the initial processing of GLUT4 to ensure it can respond to Insulin, a pathway defective in the case of Type 2 Diabetes (T2D). During this work I began to use myotubes differentiated from human muscle myoblasts and to experiment with mechanical stimulation using electrochemical exercise mimetics, with the aspiration of understanding how muscle, which is a mechanically active tissue, regulates its protein composition to maintain homeostatic balance over a life course.

In my current work, I am continuing to develop my interest in the mechanobiological and protein trafficking aspects of muscle cell biology by examining a trafficking defect in FSHD patient derived myotubes. This defect affects the clearance of the mitochondrial organelle, the so-called powerhouse of the cell. As muscle is a highly energetically demanding tissue due to its mechanical function, it is hoped that understanding and targeting this pathway may lead both to new understanding about the disease mechanism of FSHD and provide potential targets for therapeutic intervention.

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