The Mali group works on the assembly mechanisms of ciliary dynein motors, and is supported by an MRC Career Development Fellowship
The Mali lab studies the assembly mechanisms of ciliary dynein motors that power the beating motion of eukaryotic cilia and flagella. A major focus in the lab is to mechanistically understand an emerging family of proteins called the Dynein Axonemal Assembly Factors or DNAAFs. Dynein mis-assembly underlies a severe incurable respiratory disease in humans called Primary Ciliary Dyskinesia (PCD).
The lab integrates cellular, biochemical and structural techniques to uncover the molecular mechanisms by which DNAAFs aid dynein motor assembly. A longer-term objective for the lab is to better understand PCD pathology to find new treatments.
Girish has had a very long-standing interest in DNAAFs and ciliary dynein assembly. He obtained his PhD in 2015 from the MRC Human Genetics Unit in Edinburgh with Prof. Pleasantine Mill, studying mouse models defective in ciliary dynein assembly (DNAAF5 and DNAAF7). This was followed by a postdoc with Dr. Andrew Carter at the MRC Laboratory of Molecular Biology in Cambridge. Here he learned biochemistry and cryo-EM and applied his cell biological skills to discover a novel ciliary dynein inhibitor which he named Shulin (aka DNAAF9). This work also led to one of the first cryo-EM structures of any ciliary dynein. For his postdoc work, Girish was awarded the LMB Brenner Postdoc Prize in late 2021. In 2022, Girish started his independent research lab as a Lecturer at the University of Bristol’s School of Biochemistry supported by a Springboard Award (Academy of Medical Sciences and Wellcome Trust). He retains an affiliation with Bristol as an Honorary Research Fellow.
On his new appointment at the Dunn School of Pathology, Girish said – “I am delighted to join the Dunn School. The lab’s major focus is ciliary dynein motor assembly but we are generally intrigued by the fundamental principles by which cells assemble other large protein machineries – this is still very much a molecular black box in cell biology. Importantly, complex mis-assembly often lies at the heart of numerous human pathologies. So we really hope that our efforts in dissecting the paradigm of ciliary dynein assembly can shed some light on more generalizable principles of assembly for other complexes relevant to human health. I think this beautifully aligns with the Dunn School’s mission of understanding the molecular and cellular mechanisms that underlie human health and disease.”