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Astbury Centre || School of Biomedical Sciences || Faculty of Biological Sciences || University of Leeds
In situ molecular structures of the mammalian brain
We are a multidisciplinary research group using mouse genetics, pharmacology, cryogenic correlated light and electron microscopy (cryoCLEM), and cryo-electron tomgraphy (cryoET). We have developed novel workflows to prepare tissues and locate molecular targets for in situ structure determination. Using these approaches we are investigating fundamental molecular mechanisms within the mammalian brain with a particular focus on the structural basis of synaptic mechanisms, memory, and Alzheimer's disease.
Synapse memory
Synapse memory
Synapses are subcellular compartments that mediate the connectivity and information transfer within neuronal circuits of the brain. The structural remodelling of the synapse is thought to mediate the acquisition of memory in the mammalian brain. Using genetic labels and cryoET we are determinaing the structural basis of these synaptic mechanisms.
Alzheimer's disease
Alzheimer's disease
Most neurodegenerative diseases are characterised by the deposition of disease-specific amyloids. We are investigating the in situ molecular structure of Alzheimer's disease amyloid pathology and synapses. We determined the first in-tissue molecular architecture of an amyloid in the mammalian brain. We also determined the first structure of a protein resolving the polypeptide fold within a tissue.
Methods development
Methods development
We are seeking to exploit the untapped potential of in situ structural biology of tissues by developing novel cryoCLEM labels and workflows. We have developed expertise in preparing tissues and cryoCLEM-guided cryoET for in situ structure determination.
News
Apr 2025. Congratulations to Maddie Gilbert on successfully defending her PhD thesis! And recognition from the Faculty of Biological Sciences with the Romaine Hervey Memorial PhD thesis prize 2025!
Jan 2025. Congratulations Maddie Gilbert on being awared the MRC UK-Japan joint Neuroscience symposium best poster prize at Awaji Island!
Oct 2024. CryoCLEM-guided cryoET of mouse brain synapses accepted in eLife!
Jul 2024. Congratulations to Maddie Gilbert, Nayab Fatima, Joshua Jenkins and Tom O'Sullivan who jointly led a study published in Nature!
Mar 2024. Congratulations newly minted Dr Charlie Lovatt on defending his PhD thesis! And the icing on the cake - awarded the McPherson PhD thesis prize 2024 from the Faculty of Biological Sciences.
Aug 2023. Our recent preprint was profiled on Alzforum. Love the opening line: "Just as the Hubble space telescope’s...". See here:
Aug 2023 Congratulations Conny Leistner on being awarded the Romaine Hervey Memorial PhD thesis prize 2023!
July 2023. Preprint is out: 'In situ cryo-electron tomography of beta-amyloid and tau in post-mortem Alzheimer's disease brain
July 2023. Save the date: We are hosting the ARUK Yorkshire Symposium on Wed 6 Sep 2023, University of Leeds. Registation (on Eventbrite) will open in a few days time....
June 2023. Together with Prof Neil Ranson and several University of Leeds celleagues, we have been awarded the funds to purchase a cryoFIB-SEM! Watch this space for tissue lamellae..
May 2023. Our recent paper was profiled on Alzforum. See here: https://www.alzforum.org/news/research-news/amyloid-jungle-plaque-fibrils-mesh-all-manner-vesicles-membranes
Apr 2023. Presented our groups work at the CCPEM Spring Symposium (presentation was recorded and will be available on Youtube soon...).
Jan 2023. Welcome Dr Joshua Jenkins starting a postdoctoral fellowship in our group.
Nov 2022. Our in-tissue amyloid pre-print is now avaiable on Biorxiv.
Sep 2022. Congratulations Dr!! Conny Leistner for successfully defending her PhD thesis.
Apr 2021. Welcome Nayab Fatima starting a postdoctoral fellowship in the our group.
Feb 2021. Group biorxiv preprint published reporting the first in-tissue molecular architecture (by cryoCLEM-guided) cryoET of adult brain synapses.
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