{"id":49,"date":"2020-04-17T11:15:15","date_gmt":"2020-04-17T10:15:15","guid":{"rendered":"https:\/\/www2.mrc-lmb.cam.ac.uk\/groups\/falcon\/?page_id=49"},"modified":"2026-02-19T17:34:21","modified_gmt":"2026-02-19T17:34:21","slug":"research","status":"publish","type":"page","link":"https:\/\/www2.mrc-lmb.cam.ac.uk\/groups\/falcon\/research\/","title":{"rendered":"Research"},"content":{"rendered":"\n<p>Neurodegenerative diseases are characterised by the pathological assembly of specific proteins into filaments within the central nervous system. Genetic studies have established a causal role for assembly in neurodegeneration. Our goal is to understand the molecular mechanisms of pathological protein assembly in motor neuron diseases (including amyotrophic lateral sclerosis) and frontotemporal dementias, two related groups of neurodegenerative diseases. We anticipate that this work will reveal strategies to target assembly for the diagnosis and treatment of these devastating diseases.<\/p>\n\n\n<div class=\"wp-block-image\">\n<figure class=\"aligncenter size-medium is-resized\"><img loading=\"lazy\" decoding=\"async\" width=\"300\" height=\"206\" src=\"https:\/\/www2.mrc-lmb.cam.ac.uk\/groups\/falcon\/wp-content\/uploads\/sites\/28\/Ryskeldi-Falcon_web_image1-1-300x206.png\" alt=\"\" class=\"wp-image-708\" style=\"aspect-ratio:1.4563106364630354;width:732px;height:auto\" srcset=\"https:\/\/www2.mrc-lmb.cam.ac.uk\/groups\/falcon\/wp-content\/uploads\/sites\/28\/Ryskeldi-Falcon_web_image1-1-300x206.png 300w, https:\/\/www2.mrc-lmb.cam.ac.uk\/groups\/falcon\/wp-content\/uploads\/sites\/28\/Ryskeldi-Falcon_web_image1-1-1024x702.png 1024w, https:\/\/www2.mrc-lmb.cam.ac.uk\/groups\/falcon\/wp-content\/uploads\/sites\/28\/Ryskeldi-Falcon_web_image1-1-768x526.png 768w, https:\/\/www2.mrc-lmb.cam.ac.uk\/groups\/falcon\/wp-content\/uploads\/sites\/28\/Ryskeldi-Falcon_web_image1-1-1536x1053.png 1536w, https:\/\/www2.mrc-lmb.cam.ac.uk\/groups\/falcon\/wp-content\/uploads\/sites\/28\/Ryskeldi-Falcon_web_image1-1.png 1703w\" sizes=\"auto, (max-width: 300px) 100vw, 300px\" \/><figcaption class=\"wp-element-caption\">Cryo-EM structure of heteromeric filaments of TDP-43 and annexin A11 in frontotemporal lobar degeneration type C (Arseni <em>et al.<\/em>, Nature, 2024).<\/figcaption><\/figure>\n<\/div>\n\n\n<p>We determine the structures of pathological protein assemblies in neurodegenerative diseases using electron cryomicroscopy (cryo-EM). We have shown that TAR DNA-binding protein 43 (TDP-43) forms distinct amyloid filament structures in different diseases. We have discovered previously unknown pathological assemblies, including amyloid filaments of TATA-binding protein-associated factor\u200915 (TAF15) and heteromeric filaments of TDP-43 and annexin A11. These findings have transformed our understanding of the molecular basis of several neurodegenerative diseases and introduced new targets for diagnosis and therapy.<\/p>\n\n\n<div class=\"wp-block-image\">\n<figure class=\"aligncenter size-full is-resized\"><img loading=\"lazy\" decoding=\"async\" width=\"484\" height=\"568\" src=\"https:\/\/www2.mrc-lmb.cam.ac.uk\/groups\/falcon\/wp-content\/uploads\/sites\/28\/Screenshot-2023-06-19-at-18.26.21.png\" alt=\"\" class=\"wp-image-417\" style=\"aspect-ratio:0.8521175750383384;width:370px;height:auto\" srcset=\"https:\/\/www2.mrc-lmb.cam.ac.uk\/groups\/falcon\/wp-content\/uploads\/sites\/28\/Screenshot-2023-06-19-at-18.26.21.png 484w, https:\/\/www2.mrc-lmb.cam.ac.uk\/groups\/falcon\/wp-content\/uploads\/sites\/28\/Screenshot-2023-06-19-at-18.26.21-256x300.png 256w\" sizes=\"auto, (max-width: 484px) 100vw, 484px\" \/><figcaption class=\"wp-element-caption\">Cryo-ET of a brain extracellular vesicle from an individual with Alzheimer\u2019s disease containing tau filaments (magenta) tethered to the limiting membrane (yellow). Internal vesicles are shown in cyan (Fowler, Behr <em>et al.<\/em>, Nature Neuroscience, 2025).<\/figcaption><\/figure>\n<\/div>\n\n\n<p>We study pathological protein assembly in its cellular and tissue contexts using molecular-resolution electron cryotomography (cryo-ET) and targeted proteomics. This has revealed unexpected molecular environments and interactions that may play important roles in assembly and neurodegeneration. We are using the knowledge gained through these studies to develop model systems that recapitulate disease-characteristic filament structures. Such models are required to further investigate the molecular mechanisms of neurodegenerative diseases.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Neurodegenerative diseases are characterised by the pathological assembly of specific proteins into filaments within the central nervous system. Genetic studies have established a causal role for assembly in neurodegeneration. Our goal is to understand the molecular mechanisms of pathological protein assembly in motor neuron diseases (including amyotrophic lateral sclerosis) and frontotemporal dementias, two related groups [&hellip;]<\/p>\n","protected":false},"author":11,"featured_media":0,"parent":0,"menu_order":2,"comment_status":"closed","ping_status":"closed","template":"","meta":{"_genesis_hide_title":false,"_genesis_hide_breadcrumbs":false,"_genesis_hide_singular_image":false,"_genesis_hide_footer_widgets":false,"_genesis_custom_body_class":"","_genesis_custom_post_class":"","_genesis_layout":"","footnotes":""},"categories":[],"class_list":{"0":"post-49","1":"page","2":"type-page","3":"status-publish","5":"entry"},"featured_image_src":null,"featured_image_src_square":null,"_links":{"self":[{"href":"https:\/\/www2.mrc-lmb.cam.ac.uk\/groups\/falcon\/wp-json\/wp\/v2\/pages\/49","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www2.mrc-lmb.cam.ac.uk\/groups\/falcon\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/www2.mrc-lmb.cam.ac.uk\/groups\/falcon\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/www2.mrc-lmb.cam.ac.uk\/groups\/falcon\/wp-json\/wp\/v2\/users\/11"}],"replies":[{"embeddable":true,"href":"https:\/\/www2.mrc-lmb.cam.ac.uk\/groups\/falcon\/wp-json\/wp\/v2\/comments?post=49"}],"version-history":[{"count":19,"href":"https:\/\/www2.mrc-lmb.cam.ac.uk\/groups\/falcon\/wp-json\/wp\/v2\/pages\/49\/revisions"}],"predecessor-version":[{"id":711,"href":"https:\/\/www2.mrc-lmb.cam.ac.uk\/groups\/falcon\/wp-json\/wp\/v2\/pages\/49\/revisions\/711"}],"wp:attachment":[{"href":"https:\/\/www2.mrc-lmb.cam.ac.uk\/groups\/falcon\/wp-json\/wp\/v2\/media?parent=49"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www2.mrc-lmb.cam.ac.uk\/groups\/falcon\/wp-json\/wp\/v2\/categories?post=49"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}