Dr Clinton Lau

Position

Stipendary Lecturer in Biochemistry

Qualifications

MBiochem(Oxford); DPhil (Oxford)

Academic positions

Stipendary Lecturer in Biochemistry, Brasenose College
Wellcome Career Development Fellow, Department of Biochemistry

Academic background and previous positions

I moved from Leeds to read Biochemistry at the University of Oxford for my undergraduate degree, studying at New College. During this I fell in love with how a protein's structure relates to its function. For my DPhil in the Higgins Lab, I studied how diverse proteins from the malaria parasite, Plasmodium falciparum, interact with a particular human receptor. I then moved to Cambridge to work with Andrew Carter at the MRC LMB. Here I sought to understand how the molecular motor dynein can bind its diverse cargos, which it transports vast distances within cells in the body. Through these previous positions I gained structural biology tools such as cryo-EM, as well as biochemical and biophysical techniques to study protein function in vitro such as single-molecule TIRF assays.

Undergraduate teaching areas

Structural Biology, Cellular transport, Protein biochemistry and biophysics.

Research interests

I run a lab in the Department of Biochemistry to research how the malaria-causing parasite, Plasmodium falciparum, uses cytoskeletal filaments to organise its cellular components. We seek to understand the structure and function of these components using techniques such as single particle cryo-electron microscopy and single-molecule TIRF microscopy.

Cellular organisation is important for all organisms. For Plasmodium falciparum, the specialised machinery required to invade its human host is at one end of the cell, whereas its nucleus, mitochondria and other organelles are held toward at the other. Many proteins will likely be used to set up and maintain this striking organisation, but only some of them are known. In higher eukaryotes, cell organisation is underpinned by its cytoskeleton, which forms a complex network of filaments that extends throughout the cell. In contrast the Plasmodium falciparum parasite maintains a much reduced cytoskeleton, which, though simplified, is still important for cell function. This is exemplified by the parasite's microtubules, cytoskeletal elements formed from the protein tubulin. In the blood-stage of the parasite life cycle, the parasite maintains two tubulin-based elements: centriolar plaques that are responsible for mitosis, and a small stable microtubule array that is rooted at the apex of the parasite, reaching back along the periphery of the cell towards the nucleus. Deleting tubulin results in parasites with aberrant organisation unable to invade host cells.

To interact with the rest of the cell microtubules recruit a myriad of microtubule-binding proteins, including molecular tethers and motors. How these proteins function in parasites is not completely understood. We will dissect the function of proteins that bind to microtubules, as well as to other cytoskeletal elements, to see how they contribute to the organisation of the malaria parasite. Our research will contribute our understanding of how cytoskeletal proteins organise the eukaryotic cell, as well as identify targets future antimalarial therapeutic research.

Selected publications

AI told you so: navigating protein structure prediction in the era of machine learning.
Sami Chaaban, Giedrė Ratkevičiūtė, Clinton Lau; Biochem (Lond) 2024; doi: https://doi.org/10.1042/bio_2024_118 

Molecular mechanism of dynein-dynactin complex assembly by LIS1.
Singh K*, Lau CK*, Manigrasso G, Gama JB, Gassmann R, Carter AP. Science. 2024 Mar 29; https://doi.org/10.1126/science.adk8544 

Cryo-EM reveals the complex architecture of dynactin’s shoulder and pointed end.
Lau CK, O’Reilly FJ, Santhanam B, Lacey SE, Rappsilber J, Carter AP. EMBO J. 2021 Mar 18;e106164.

Shulin packages axonemal outer dynein arms for ciliary targeting.
 Mali GR*, Abid Ali F*, Lau CK*, Begum F, Boulanger J, Howe JD, Chen ZA, Rappsilber J, Skehel M, Carter AP. Science. 2021 Feb 26;371(6532):910-916.

Cryo-EM shows how dynactin recruits two dyneins for faster movement.
Urnavicius L*, Lau CK*, Elshenawy MM, Morales-Rios E, Motz C, Yildiz A, Carter AP. Nature. 2018 Feb 7;554(7691):202-206.

Structural conservation despite huge sequence diversity allows EPCR binding by the PfEMP1 family implicated in severe childhood malaria.
Lau CK*, Turner L*, Jespersen JS, Lowe ED, Petersen B, Wang CW, Petersen JE, Lusingu J, Theander TG, Lavstsen T, Higgins MK. Cell Host Microbe. 2015 Jan 14;17(1):118-29.

Link

https://laulab.web.ox.ac.uk/