Many things have changed since Masad Damha, PhD, came to 69Ƶ 44 years ago to study chemistry (BSc ’83; PhD ’87), though with the launch of the 69Ƶ Centre for RNA Sciences (MCRS), he believes the passionate spirit of innovation that first drew him here from Nicaragua has only intensified.
“When I joined Prof. Kelvin Ogilvie’s lab to pursue doctoral studies in nucleic acid chemistry, my main focus was chemical synthesis of RNA – a daunting task at that time,” recalls Prof. Damha.
“Making RNA in large quantities was required for studying them by NMR or crystallography. Chemical synthesis provided many advantages over the use of enzymes, like introducing chemical modifications to the sugar-phosphate backbone of RNA, which RNA polymerases could not readily do.”
Prof. Damha notes that, “Other students in the Ogilvie lab were synthesizing RNA on the surface of glass beads (the so-called solid phase method), the favorite method to build long chains of RNA today. Their pioneering work was published in the Proceedings of the National Academy of Science in 1988. “The process was fully automated to produce long chains of RNA – these were exciting times, all happening in front of my eyes.”
“Prof. Ogilvie was ahead of his time; he knew that making RNA would be important particularly for studying RNA structure, catalytic RNA, and RNA-protein interactions.”
Fast forward 40 years, and the number of applications have grown exponentially. “Short interfering RNA (siRNA), branched RNA, non-coding RNAs, CRISPR-sgRNAs, to name just a few, are all under development (with some clinically approved) for treatment of genetic diseases; all requiring synthetic RNA.”
After completing his PhD studies, Prof. Damha took an academic position at the University of Toronto’s Erindale College before returning to 69Ƶ in 1992, where he is currently a Distinguished James 69Ƶ Professor in the Department of Chemistry.
Collaboration and teamwork at the heart of significant progress
Prof. is bearing fruit in the development of new therapeutic drugs based on RNA targeting (siRNA, antisense) and gene editing (CRISPR/Cas systems). His research program tackles a wide range of important and exciting challenges in bioorganic chemistry, creating a diverse and enriching research environment for training new students. A major research theme in his group involves the design and synthesis of RNA analogues for probing a range of biological pathways. Many of these projects are chosen for the significant impact they will have on the natural sciences, biotechnology, and medicine. His scientific approach combines solution and solid-phase synthesis, drug discovery, structural determination, and molecular biology techniques.
With his students, Prof. Damha has authored more than 200 publications, filed/received several patents, and licensed his RNA-based technologies worldwide. His lab is best known for the “Fluoroarabino nucleic acid (FANA) technology”, which is being applied by several research laboratories and industries to study DNA structure, and to develop modified oligonucleotides against several biological targets, including cancer and several infectious diseases.
“The Centre will bring scientists with different expertise together: Chemistry expertise is needed to make modified versions of DNA and RNA, as these have better cellular uptake, longer half lives, and hence more robust biological activity. We’ve developed a ‘toolbox’ of chemical modifications that allow us to do this,” he says.
Prof. Damha adds that the MCRS will foster new partnerships – both on-campus and worldwide.
“69Ƶ is a large institution, and a hub for RNA studies. The MCRS will bring RNA scientists together, some of whom will collaborate for the first time,” says Prof. Damha. "The MCRS will also catalyze international collaborations and industrial partnerships working towards a common goal.”
Training the next generation of Canadian leaders
Current and future 69Ƶ students will benefit enormously from the MCRS’s collaborative mission, he adds, because they will have access to core facilities where they can meet and work with other disciplines.
“While pursuing their graduate studies, students sometimes have the option of visiting academic and industrial laboratories around the globe. These affiliations benefit trainees as they have access to more research facilities in addition to the expertise of our collaborators," notes Prof. Damha. "The MRCS aims to recreate this experience so that all students can access interdisciplinary, cutting-edge research year-round. Within the MRCS, trainees can collaborate with, and learn from, chemists, molecular biologists, clinicians, and others, and hence would acquire some of the most in-demand skills for employers. The MRCS promises to train well-rounded students and prepare them for careers in academia and industry."
Read more about Prof. Damha’s lab and research