Nucleic Acids

Date: May 25, 2023 2:00 pm (ET)


  • Maureen McKeague
    McGill University
  • Rajwinder Kaur
    University of Lethbridge

Maureen McKeague
McGill University

Title: DNA, RNA, and modified aptamer biosensors

The oligonucleotide equivalents of antibodies, known as aptamers, have emerged as potential molecular recognition rivals. Aptamers possess several ideal properties including chemical stability, in vitro selection, and lack of batch-to-batch variability. These properties have motivated the incorporation of aptamers into a wide variety of analytical, diagnostic, and therapeutic applications. This presentation will examine the work of our group in the selection, characterization, and application of aptamers as biosensors.

Bio: Assistant Professor Maureen McKeague obtained a BSc in Biochemistry and Biotechnology (2007), followed by a PhD in Chemistry (2012) both at Carleton University. Her research applied DNA nanotechnology to detect food toxins. She wanted to apply her interest in nucleic acids to the newer field of “synthetic biology”, so she moved to the Department of Bioengineering at Stanford University in California from 2012-2016 for an NSERC postdoctoral fellowship award. She then transitioned to ETH Zurich in Switzerland for 2 years as a senior researcher in the Department of Health Sciences and Technology. Here, she studied the biological relevance of alkylating DNA damage in mutagenesis and carcinogenesis. At the end of 2018, she joined McGill University as a unique joint appointee in both the Department of Pharmacology and Therapeutics and the Department of Chemistry. She is currently the Canada Research Chair in Genomic Chemistry. Her lab is interested in developing nucleic acid therapeutics and biosensors.

Rajwinder Kaur
University of Lethbridge

Title:  Exploring the versatility of metallonucleases using a multiscale computational approach

The phosphodiester linkage is a highly stable bond that is ubiquitous in biological systems. For example, the remarkable resistance of the phosphodiester backbone in nucleic acids to cleavage is essential for the storage of genetic information and proper cell function. Nevertheless, there are many instances in biology and biotechnology in which cleavage of the nucleic acid backbone is necessary. For example, DNA phosphodiester bond hydrolysis is critical to repair nucleobase damage or abasic sites to maintain genetic integrity, while cleavage in RNA is critical for quality control during protein synthesis. Furthermore, nucleic acid backbone hydrolysis can be exploited in bioindustries for DNA amplification and shuffling in genetic engineering. Nucleases are a broad class of enzymes that facilitates the challenging phosphodiester bond cleavage by increasing the reaction rate by a factor of 1017. Many nucleases rely on metals to enhance catalysis, with the role of the metal ion(s) being a topic of debate. While the two-metal mediated mechanism has been universally well accepted for the bond cleavage, support in favor of one metal being enough for catalysis has been growing in recent years. Although there is an abundance of computational studies on nucleases that use two metal ions, the atomic-level details of the one-metal mediated chemistry are poorly understood. This work provides fundamental information regarding how different endonucleases use one or two metals to efficiently catalyze the phosphodiester bond hydrolysis in nucleic acids and how diversity in active site architectures leads to different chemical pathways for the same reaction. Specifically, we have used a mixed computational approach that includes QM cluster, molecular dynamics (MD) simulations, and quantum mechanics–molecular mechanics calculations (QM/MM) to provide clues about endonuclease function. The mechanistic details uncovered by this work will open the door for applications in disease diagnostics, genetic engineering, and designing small molecule inhibitors to target a host of diseases.

Bio: Rajwinder Kaur. I am a final year PhD student in Dr. Stacey Wetmore’s lab. My research focuses on understanding the catalytic pathways used by metallonucleases.