PhD project

PhD project

Mechanistic studies on protein folding and assembly of ciliary dynein motors

Supervisor: Girish Ram Mali

 

All proteins are made up of amino acids, the building blocks of cells, which are strung together to make a peptide chain. Polypeptide chains get sculpted into their 3‐dimensional shapes to specify a cellular function by additional proteins called molecular chaperones and assembly factors. For ciliary dyneins, a clinically important class of motor proteins that power the beating motion of cilia and flagella in our bodies, 19 dynein assembly factors have been identified. Loss of ciliary dyneins leads to a severe incurable human respiratory disease called Primary Ciliary Dyskinesia.

How chaperones and dynein assembly factors cooperate to fold the dynein peptide chains into their intricate 3D shapes and then assemble them together into larger holocomplexes is an unsolved question in cell biology. It is also central to understanding human pathology as disease causing mutations often disrupt the assembly process. In this project we will combine cellular, structural and biochemical techniques to gain insights into the dynein folding and assembly process with a goal to dissecting disease mechanisms.

 

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: 7554/eLife.34389
  • 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

Available PhD projects

Over 30 groups work at the Dunn School to uncover the molecular and cellular mechanisms underlying disease. Discover which research groups are accepting students for our next round of applications.

Our PhD course

Doing a DPhil in Molecular Cell Biology in Health and Disease at the Dunn School is the best way to start your career.