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Lab Life: Sleigh Lab

We go behind the scenes in Dr James Sleigh's lab to hear about their research, their techniques, and moving to Grays Inn Road .

Dr. James Sleigh is an MRC Senior Non-Clinical Fellow and his laboratory uses mouse and iPSC models to study neuromuscular diseases. We go behind the scenes to hear about their research, their techniques, and moving to Grays Inn Road.

image of Sleigh Lab at UCL

We are based in the Department of Neuromuscular Diseases, currently on the fifth floor of Queen Square House, and our focus is genetic peripheral neuropathy/Charcot-Marie-Tooth disease (CMT) – a heterogeneous collection of diseases impacting motor and sensory neurons. Also affiliated with the UK Dementia Research Institute, we work on several other conditions affecting the neuromuscular system, including amyotrophic lateral sclerosis.

We are fascinated by how mutations in widely-expressed genes can cause selective peripheral nerve degeneration. By improving our understanding of the molecular and cellular mechanisms underpinning this phenomenon, we aim to develop novel, targeted therapies for these devastating disorders.

mouse neuromuscular junctions cell image

At the moment, there are six of us – PI James, postdocs David and Ellie, PhD students Qiuhan and Sijiang, and PhD rotation student Louisa – and we are welcoming two new postdocs in October this year. We aim to continue this growth at Grays Inn Road, where we hope to make the most of the many core facilities on offer. Members of the team have worked at different institutions where such shared initiatives really boosted productivity and helped to streamline the research.

Principally funded by long-term fellowships from the Medical Research Council, we pair mice and primary neuronal cultures with stem cell-based models of neuromuscular diseases to identify underlying pathomechanisms. We also regularly collaborate closely with some of the world-class CMT clinicians at the IoN.

One of our main strengths is our intravital approach that permits in vivo imaging of axonal transport, which is a dynamic cellular process that often becomes perturbed in neurological diseases. We have started to perform simultaneous live imaging of different axonal cargoes (endosomes and mitochondria) and are excited to begin studying how they interact within healthy and pathological peripheral nerves. Additionally, we harness fine dissection techniques to perform careful comparative anatomical assessments of key components of the peripheral nervous system, e.g., the neuromuscular junction and dorsal root ganglia.

Mouse dorsal root ganglion cell image

Based on our more recent findings, we have also begun to create pre-clinical AAV therapies that selectively target muscle. These activities have benefitted greatly from the gene therapy experts, translational resources and key partnerships across the IoN and UCL more broadly – including ACCELERATE, the GeneTxNeuro Vector core facility, the IoN’s Translational Research and Enterprise Committee and UCLB.

Mouse neuromuscular junctions and vasculature cell image

We are a highly collaborative team that enjoy working with others and sharing our expertise, so cannot wait to move into the new building, which will truly enhance these opportunities and lead to a cohesive and pioneering centre for translational neuroscience. We already have lots of excellent collaborators throughout the IoN and further afield, and look forward to the additional interactions and opportunities that the dual hub will bring.

At Grays Inn Road, we will be located on level 2, close to the Genetic Therapy Platform, which we will undoubtedly be making great use of. We are already benefiting from recently purchased confocal microscopes that will be moving to the new building, and from the shared cell culture hoods that have been successfully trialled in our department.

When we are all together in the dual hub, it is going to be transformative!