Miratul Muqit, Wellcome Trust Senior Clinical Fellow and Honorary Consultant Neurologist at the MRC Protein Phosphorylation and Ubiquitylation Unit of the University of Dundee is among 59 medical researchers who have been elected to join the Academy of Medical Sciences one of the UK’s most prestigious medical academies.
Fellowship of the Academy is based on exceptional contributions to the medical sciences. Miratul’s election recognises his major contributions to the understanding of the causes of Parkinson’s disease. Miratul’s research showed that in response to agents that damage mitochondria, PINK1 is stabilised and activated and phosphorylates and activates the Parkin ubiquitin E3 ligase. Miratul found that in addition to phosphorylating Parkin, PINK1 strikingly directly phosphorylates ubiquitin, which acts as a powerful activator of Parkin. He also found that PINK1 regulates the phosphorylation of a new site on Rab proteins (Ser 111).
More recently, Miratul has discovered key phosphorylation sites on PINK1 that regulate activation including Ser 167, Ser 228 and Cys 412 (one of the first examples of Cys phosphorylation). He has also undertaken further in-depth experiments that define the mechanism by which PINK1 is recruited to damaged mitochondria by binding to the TOM complex via a novel alpha-helical N-terminal domain and how this triggers their removal by activating mitophagy. Overall, his research has illuminated the function PINK1 and Parkin and how mutations in these genes lead to the build-up of damaged mitochondria in brain cells resulting in Parkinson’s.
Miratul has also helped develop and characterise Phospho-antibodies that recognise the PINK1 phosphorylated forms of ubiquitin, Parkin, and Rab proteins as well as PINK1 autophosphorylation sites. These have become major biomarkers in the field of research and are currently being tested in patients to diagnose and monitor Parkinson’s. His work has also revealed new strategies to treat Parkinson’s that are being explored by biotechnology and pharmaceutical companies.
Commenting on the award Professor Muqit said “As a physician-scientist it is a great honour to be elected to the Academy of Medical Sciences. The award truly recognises the tremendous contributions of the many talented researchers who have worked in my lab; all my collaborators; and the many charities and funding agencies who have supported our work notably the Wellcome Trust and the Michael J Fox Foundation. Our work is also greatly influenced by the people affected with Parkinson’s who I care for in my clinics and who I have the privilege to meet and interact with outside through our public engagement activities.”
He added “Whilst our work has provided a clearer picture of how Parkinson’s develops, we continue to work tirelessly to apply this knowledge to find better treatments that can slow or stop Parkinson’s in its tracks.”
Professor Dario Alessi, Director of the MRC PPU added “I warmly congratulate Miratul for this very prestigious and well merited award. His contribution to deciphering how mutations in the gene PINK1 causes Parkinson’s disease has been immense. Miratul is one of the few neurologists who have a fantastic knowledge and expertise in both medical as well as basic research arenas.”
Miratul is the third member of the MRC PPU to receive this distinction after Philip Cohen and Dario Alessi.