PhD project

PhD project

Chaperone mediated assembly of ciliary dynein motors

Supervisor: Girish Ram Mali

All cellular proteins are made as long strings of amino acids called polypeptide chains. How these chains get folded into their unique 3‐dimensional shapes so they can perform their unique cellular functions remains an outstanding question in biology. It is known that cells use proteins called molecular chaperones to assist protein folding.

Our lab focuses on understanding the folding, assembly and trafficking of ciliary dynein motors that power the beating motion of eukaryotic cilia and flagella. A newly discovered family of proteins called Dynein Axonemal Assembly Factors (DNAAFs) cooperates with molecular chaperones to shepherd dynein assembly.

A key focus of this project is to dissect how chaperones and DNAAFs interact. Understanding their interactions is central to human biology as mis-folding/mis-assembly of ciliary dynein’s is a leading cause of infertility and a severe respiratory illness in humans called Primary Ciliary Dyskinesia (PCD).

We use a diverse set of techniques in the lab including cell culture, bioimaging, proteomics, biochemistry and structural studies. This project will combine several of these techniques to elucidate the molecular mechanisms of chaperones and DNAAFs in folding and assembling dynein motors.

Keywords:

  • Biochemistry, Cell Biology / Development, Genetics, Molecular Biology, Structural Biology

Publications:

  • Mali GR et al., Shulin packages axonemal outer dynein arms for ciliary targeting. Science. 2021 Feb 371 (6532), 910–916. DOI: 10.1126/science.abe0526
  • Mali GR et al., ZMYND10 functions in a chaperone relay during axonemal dynein assembly. Elife. 2018 Jun 19; 7:e34389. DOI: 10.7554/eLife.34389
  • Diggle CP et al. HEATR2 plays a conserved role in assembly of the ciliary motile apparatus. PLoS Genet. 2014 Sep 18; 10(9): e1004577. DOI: 10.1371/journal.pgen.1004577
  • King SM. Cytoplasmic factories for axonemal dynein assembly. J Cell Sci. 2021 Aug 1;134(15):jcs258626. DOI: 10.1242/jcs.258626.

Mali lab

Investigating how cells assemble axonemal dyneins, in particular the role of DNAAFs in this process

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