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Knott Lab research

CollaborationsStudent research projects | Publications

About Dr Gavin Knott

Gavin earned his Ph.D. from the University of Western Australia in 2016 where he studied under Prof. Charlie Bond and Prof. Archa Fox. After completing his PhD., he moved to the University of California Berkeley where he worked under the supervision of Nobel Laureate Prof. Jennifer Doudna. In 2021, he started his own independent research lab in the Department of Biochemistry and Molecular Biology in the Biomedicine Discovery Institute at Monash University.

With a long-standing passion for RNA biology, Gavin’s  work has focused on understanding how evolution has selected for structurally and functionally diverse proteins that recognize one of biologies most remarkable polymers, RNA. His lab uses cutting edge biochemistry and structural biology (Cryo-EM/X-ray crystallography) to better understand how bacterial and viral proteins target nucleic acids during infection. His research group seeks to harness the evolved diversity of innate and adaptive immune systems for use in biotechnology and therapeutic applications.


Our research

Bacteria are embroiled in a constant struggle with virulent bacteriophages. This battle for survival spans millions of years of evolution. Throughout this struggle, bacteria and phages have evolved remarkably diverse strategies to protect themselves. Using cutting edge structural biology and biochemical techniques, the Knott Lab seeks to uncover the molecular details of how novel bacterial and viral immune systems specifically sense foreign viral RNA to protect against infection.

Current projects

1. CRISPR-Cas systems for direct RNA detection

Upon detection of phage RNA, a bacterium often drives abortive infection - a cellular response that offers a community herd immunity to viral infection. CRISPR-Cas13 is a programmable RNA-guided nuclease that upon specific recognition of a viral RNA drives abortive infection by degrading the transcriptome. Using structural biology, we seek to understand the molecular details of this process with an eye to apply our findings to the effective implementation of Cas13 as a tool in CRISPR-based RNA detection and diagnostics.

2. Innate immune recognition of viral nucleic acids

The recognition of foreign viral RNA requires bacteria to discriminate self from non-self.  Bacteria do this using a combination of specific structures, patterns of nucleotide modification, and/or protein factors. We are investigating families of bacterial innate immune systems that home in on these molecular differences to identify viral transcripts and protect the host from infection. With a structural and biochemical understanding of how these novel systems function, we seek to apply them as biotech tools.

3. Precision RNA-targeting with CRISPR

Bacteria have evolved strategies to precisely interfere with phage replication through specific nuclease activity targeted to phage transcripts. These DNA or RNA guided nucleases are poorly understood as prokaryotic adaptive immune systems. We are leveraging structural biology to uncover how they are steered towards viral RNA targets for precise interference. With a better appreciation of their mechanisms, we are looking to apply them as tools for the study of specific RNA targets in bacterial, plant or human cells.

Visit Dr Knott’s Monash research profile to see a full listing of current projects.

Techniques/expertise

  • CRISPR-Cas biotechnology
  • Cryo-electron microscopy
  • X-ray crystallography
  • RNA and protein biochemistry
  • Bioinformatics

Collaborations

We collaborate with many scientists and research organisations around the world. Click on the map to see the details for each of these collaborators (dive into specific publications and outputs by clicking on the dots).


Student research projects

The Knott Lab offers a variety of Honours, Masters and PhD projects for students interested in joining our group. There are also a number of short term research opportunities available.

Please visit Supervisor Connect to explore the projects currently available in our Lab.