Richard Wheeler

The role of motility and cell shape in Leishmania parasite pathogenicity.

Richard Wheeler is a Chancellors Fellow at the University of Edinburgh. Following a BA and MSci in Natural Sciences (specialising in biochemistry) at the University of Cambridge he moved to the University of Oxford, where he did a DPhil as part of the Wellcome Trust Infection, Immunology and Translational Medicine studentship. He finished his DPhil in 2012 and followed it with a postdoctoral with Keith Gull (Sir William Dunn School of Pathology, University of Oxford) and a Wellcome Trust Sir Henry Wellcome postdoctoral fellowship partly spent between the Max Planck Institute for Molecular Cell Biology and Genetics (with Tony Hyman) and the Dunn School. 

portrait photo of Richard Wheeler
Richard Wheeler

Richard was awarded a Sir Henry Dale Fellowship from the Wellcome Trust to found his research group in 2018, as part of the Nuffield Department of Medicine in the University of Oxford, before moving to Edinburgh in 2024.

Ulrich Dobramysl (Postdoc)


The Parasite: Leishmania cause a serious human disease, Leishmaniasis, in many tropical and sub-tropical regions of the world. They are single celled eukaryotic parasites which are carried in the gut of sandflies. When a sandfly bites a person the parasites are transmitted in the fly's saliva and can infect their macrophages. Leishmania are a tough and persistent parasite and, depending on the species, can cause symptoms from mild but disfiguring skin lesions to death.

The Research: The main research focus of the lab is the flagellum: The 'tail' of the parasite that they use to swim. However, we are also interested in wider questions of how the parasite generates and controls its shape, how this adapts the parasite cells to be effective pathogens and how they evolved from non-pathogenic species.

Wider research interests include the related parasites Trypanosoma which also cause human disease. General questions about how eukaryote cells organise their internal structure are also of particular interest.

Approaches: The main methods are classic cell biology, molecular biology and biochemistry techniques, supported by mathematical and computational simulation, biophysics, and automated image analysis. Advanced microscopy coupled with semi and fully automated image analysis are particular specialities of the lab.


analysis of intra flagella transport in beating flagella

Figure: Quantitative intraflagellar transport (IFT) analysis in live beating flagella. 
(A) Still frame from a 200 Hz dual-color, high-frame-rate video micrograph of a cell expressing 3×mNG::IFT172 (IFT marker) and SMP1::mCh (flagellar membrane marker). (B) Still frame from a 200 Hz dual-color, high-frame-rate video micrograph of a cell expressing 3×mNG::IFT172 (IFT marker) in fluorescence and phase contrast. (C) SMP1::mCh image used for flagellum tracing (red) and the flagellum midline (white line) determined by thresholding. (D) Digitally straightened view of the flagellum showing the same frame as in A straightened using the midline in B. (E) Tangent angle at different distances along the flagellum, represented as a graph and a color-coded bar, showing the same frame as inA. (F) Kymograph of flagellum tangent angle over time for a 100-frame section of the dual-color, high-frame-rate video micrograph. (G) Power spectrum over time, calculated from the flagellum tangent angle kymograph, for the full-length video micrograph. (H) Kymograph of 3×mNG::IFT172 and SMP1::mCh fluorescent signal over time for the full-length video micrograph. IFT trains are readily visible. Animated version of A and D–H in Video 2.

Doran MH, Niu Q, Zeng J, Beneke T, Smith J, Ren P, Fochler S, Coscia A, Höög JL, Meleppattu S, Lishko PV, Wheeler RJ, Gluenz E, Zhang R, Brown A (2025)“Evolutionary adaptations of doublet microtubules in trypanosomatid parasites.” Science 387(6739):eadr5507 doi:10.1126/science.adr5507

Fort C, Walker BJ, Baert L, Wheeler RJ (2025)
“Proteins with proximal-distal asymmetries in axoneme localisation control flagellum beat frequency.” Nat Commun 16(1):3237
doi:10.1038/s41467-025-58405-1

Uechi H, Sridharan S, Nijssen J, Bilstein J, Iglesias-Artola JM, Kishigami S, Casablancas-Antras V, Poser I, Martinez EJ, Boczek E, Wagner M, Tomschke N, de Jesus Domingues AM, Pal A, Doeleman T, Kour S, Anderson EN, Stein F, Lee HO, Zhang X, Fritsch AW, Jahnel M, Fürsch J, Murthy AC, Alberti S, Bickle M, Fawzi NL, Nadler A, David DC, Pandey UB, Hermann A, Stengel F, Davis BG, Baldwin AJ, Savitski MM, Hyman AA, Wheeler RJ (2025) “Small-molecule dissolution of stress granules by redox modulation benefits ALS models.” Nat Chem Biol doi:10.1038/s41589-025-01893-5

Gray S, Fort C, Wheeler RJ (2024) “Intraflagellar transport speed is sensitive to genetic and mechanical perturbations to flagellar beating.” J Cell Biol 223(9):e202401154 doi:10.1083/jcb.202401154

Karen Billington, Clare Halliday, Ross Madden, Philip Dyer, Amy Rachel Barker, Flávia Fernandes Moreira-Leite, Mark Carrington, Sue Vaughan, Christiane Hertz-Fowler, Samuel Dean, Jack Daniel Sunter, Richard John Wheeler & Keith Gull. "Genome-wide subcellular protein map for the flagellate parasite Trypanosoma brucei" Nature Microbiology, doi:10.1038/s41564-022-01295-6

López-Escobar L, Hänisch B, Halliday C, Ishii M, Akiyoshi B, Dean S, Sunter JD, Wheeler RJ, Gull K (2022) “Stage-specific transcription activator ESB1 regulates monoallelic antigen expression in Trypanosoma brucei.” Nat Microbiol doi:10.1038/s41564-022-01175-z

 


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