Alexander Russell

Dissecting a role for ZAK-beta in skeletal muscle development using genetics and embryology in zebrafish and Xenopus

About me

I graduated with a first class degree with honours from Newcastle University in Biomedical Sciences. My undergraduate research project involved investigating the effect of IL-3 signalling in human peripheral blood mononuclear cells, in Professor John Isaacs’s lab. During my degree, I also undertook a year in industry at Allergan Biologics, where I was involved in the research and development of downstream drug purification. I was also involved in optimising procedures for robotics and high-throughput microfluidic capillary electrophoresis for glycan analysis of antibodies.

My interest in researching muscle diseases came during work experience at age 16, where I shadowed scientists at the neuromuscular laboratories, Newcastle University. The research focussed on Duchene muscular dystrophy, using animal models, and I performed procedures such as injecting zebrafish embryos with morpholinos for phenotypic analysis. This opportunity piqued my interest in researching rare muscle diseases, which led to me choosing a PhD using zebrafish to model and decipher the role of a novel MAP triple kinase implicated in a congenital myopathy.

My project

My project is focused around a MAP3K that has recently been implicated in a subset of patients with a previously undiagnosed congenital myopathy. Congenital myopathies describe a collective group of inherited, heterogeneous, rare muscle diseases associated with progressive muscle wasting, chronic disability and a reduced quality of life. ZAK is a protein of which there are 2 splice isoforms in humans (ZAKα and ZAKβ) with the ZAKβ associated with myopathy.

I will be using zebrafish and Xenopus embryology to dissect role that ZAK is playing in skeletal muscle development and regeneration, as well as understanding the pathobiological mechanism. Zebrafish represent an excellent model to study muscle diseases and have been used extensively in researching muscular dystrophies and congenital myopathies. I will be using CRISPR to gene edit and knockout the ZAKα and ZAKβ isoforms in zebrafish for research into the muscle disease phenotype in zebrafish. Xenopus embryos will be used due to existing robust signal transduction assays, which provide an excellent system to dissect the molecular and cellular processes that require the ZAK signalling pathway in skeletal muscle.


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