Keith Shearwin

Associate Professor Keith Shearwin

Associate Professor/Reader

School of Biological Sciences

Faculty of Sciences, Engineering and Technology

Eligible to supervise Masters and PhD - email supervisor to discuss availability.


Overview

Our research integrates biochemistry, genetics and mathematical modelling to characterise fundamental mechanisms of gene control and how these elements are combined to create gene regulatory circuits with complex functions. Having a detailed understanding of the properties of natural regulatory circuits makes it possible to rearrange these components to build circuits with new and interesting behaviours - the emerging discipline of Synthetic Biology. We have a strong focus on using and developing mathematical modelling as a tool to advance understanding of gene regulatory mechanisms and systems, a tool that will be essential for the new ‘systems biology’ as molecular biology tries to move from characterizing the parts of cells and their simple interactions to understanding how these interactions combine to generate complex functions.  We find that the process of attempting to construct a mathematical model of a biological system is valuable in itself - helping to clarify ideas, define assumptions and identify missing information. Once a model is made, comparison of the model with available experimental data can reveal shortcomings in either, leading to changes to the model or to improved data collection or interpretation. A consistent mathematical description is a powerful tool, providing precise predictions to aid further experimental tests, and allowing rapid exploration of the range of properties of the system to generate insights into design features.

Our primary experimental systems are two E. coli bacteriophages, lambda and 186. These temperate phages can replicate their genomes using alternative developmental pathways, lysis and lysogeny, and are some of the simplest organisms to make developmental decisions. Despite their relative simplicity, the phage systems combine a wide range of gene control mechanisms in complex ways and have many lessons to teach us. Bacteriophage lambda continues to be a key model system for many molecular biological processes; phage 186 is less well characterised but provides a powerful comparison with lambda, as it achieves similar outcomes using different regulatory circuits. The fundamental biochemistry shared by all living things means that the study of any organism, from phages to humans, continues to illuminate universal principles that apply to all organisms.

Projects available
  • Phage hunting – discovering new phage against medically important bacteria
  • Protein engineering of endolysins for enhanced bacterial killing
  • Precision engineering of bacteriophage genomes
  • Directed evolution of new protein activities

 

Funding

Contract Research - Aushealth (2023)

Discovery and directed evolution of small molecule biosensors ARC Discovery Project DP230103062 (2023) Whelan, F., Shearwin, K., Potts, J. $522,724

Improving biorefineries by phage-assisted evolution of cytochrome P450 enzyme activity. BTF New collaboration scheme (2022) Shearwin, K., Bell, S., Hao, N., Whelan, F. Beltrame, L. and Harlington, A. $40,000

Biodegradation of Plastics via Bioengineered Enzyme Systems. Faculty of Sciences Research Roadmap Grant (2021) Whelan, F., Shearwin, K, Bell, S., Gillanders, B. $50,000

Engineering biosensors for smoke taint. Wine Australia top up scholarship to Alix Harlington. (2021-2023) Whelan, F., Shearwin, K., Wilkinson, K. $49,000

Engineering biosensors for wine spoilage. Wine Australia top up scholarship to Ranjith Cebreco Meemanage. (2021-2023) Whelan, F., Shearwin, K., Wilkinson, K. $49,000

Pesticide biosensor development and hybrid device integration for agricultural and environmental analytics. Sandland Bequest. (2021) Whelan, F., Shearwin, K, Bell, S., Wilkinson, K., Law, C., Santos, A. $25,000

Evolving phage derived proteins as potent anti-bacterial agents. BTF New collaboration scheme (2021) Shearwin, K.E. $30,000

Doing the sums: how circuit copy number affects genetic switches. BTF Near Miss Scheme (2021) Shearwin, K.E. (2021) $40,000

Developing orthogonal Cas/anti-Cas pairs as building blocks for genetic circuit design. CSIRO FSP Fellowship to Andrew Hao. (2017-2021) Hao, N., Shearwin, K.E., Dodd, I.B., Scott, C. $510,000

Synthetic biology tools for integration into bacterial chromosomes. ARC Discovery Grant DP160101450 (2016-2019) Shearwin, K.E. and Bikard, D. $410,000

Understanding and manipulating DNA looping in long range gene regulation. NHMRC Project Grant APP1100651 (2016-2019) Dodd, I.B., Shearwin, K.E., Sneppen, K. and Hao, N. $351,000

Flipping the switch: rational design of genetic circuits that respond to transient signals. ARC Discovery Grant DP150103009  (2015-2018) Shearwin, K.E., Dodd, I.B. and Sneppen, K. $241,000

Quantitative analysis of the DNA loop-domain model for long range regulation of transcription. Human Frontiers Science Program  RGP0051 (2009-2012) Shearwin, K.E., Dunlap, D. and Swigon, D. $1,251,000 (total)

Road rules for traffic on DNA - gene regulation by encounters between transcribing RNA polymerases and DNA-bound proteins. ARC Discovery Grant DP110101470  (2011-2013) Dodd, I.B., Shearwin, K.E., and Sneppen, K. $300,000

Synthetic Biology - The Rational Design and Construction of New Genetic Circuits. ARC Discovery Grant DP110100824 (2011-2013) Shearwin, K.E., Dodd, I.B., Finzi, L. and Sneppen, K. $300,000

Understanding and controlling PAS domain interactions in basic helix-loop-helix transcription factors. NHMRC APP627140 (2010-2012) Chapman-Smith, A., Whitelaw, M.L., Shearwin, K.E. and Dodd, I.B. $608,000

Rational design of small genetic circuits for synthetic biology. ARC Discovery Grant DP0665185 (2006-2008) Shearwin, K.E. and Egan, J.B. $368,000

Transcriptional Interference in Gene Regulatory Decisions. NIH R01 (2006-2009) Egan, J.B., Dodd, I.B. and Shearwin, K.E. $526,000

The South Australian Facility for Small and Large Molecule X-Ray Diffraction Structure Determination. ARC LIEF(2009) Sumby, C.J, Shearwin, K.E. and 26 others $560,000

Biophysical Characterisation Facility. ARC LIEF Grant LE0882382 (2008) Brooks, D.A., Shearwin, K.E. (lead CI for University of Adelaide) and 14 others $245,000

Biophysical Characterisation Facility. AIB Labs (2008) Brooks, D.A., Shearwin, K.E. (lead CI for University of Adelaide) and 14 others $50,000

ARC Australian Research Fellowship (1996-2000) Shearwin, K.E. $400,000

 

 

 
Course coordinator: Biochemistry II (2021-)
In 2023 I am teaching in the following courses

Biochemistry II Molecular and Cellular Biology (course coordinator, lectures)

Biomedical Science IIA (lectures)

Biotechnology II (lectures)

Principles and Practice of Research I (interview)

Principles and Practice of Research II (mentor)

Principles and Practice of Research III (research placements)

Molecular and Structural Biology III (lectures, tutorials, practicals)

Cancer, Stem Cells and Development (Biomed) (PBL)

Cancer, Stem Cells and Development III (essays)

Masters in Biotechnology: Advanced Research Platforms (lectures)

Honours in Biochemistry (journal club; research grant proposal and thesis assessment)

Laboratory Placements

We host 3rd year laboratory placement students each year.

2023: Amal Mostafa

2022: Sarah Eisemann, Deannon Branch, Julia Leeflang, Jayden Revink

2020: Sonia Budnikova

2019: Emma Beecroft

2018: Smriti Singh, Grace Tulysewski

2017: Khalia Primer

2016: Emi Schutz, Daniel Reed

2015: Jasmine Kelly, Mara Zeissig, Alejandra Isabel, Joe Rossi, Matilda Handsley-Davis

2014: Dominique Jackson, Queenie Tangseefa, Jade Feong, Andrew Hayes, Trang Pham

2013: Byron Shue, Jia Truong, Andelain Erickson

2012: Duncan McKenzie, Dylan Agnew, Grace De La Lande

2011: Emma Rollo, Ashleigh Paparella, Katrina Lee, Danna Lee

2010: Emily Higginson, Sofia Xuan, George Dimitroff, James Paltridge

2009: Courtney Potter

2008: Joey Puccini

2007: Veronica Bhakti, Jessica Murray

2006: Scott Berry

 

 

  • Current Higher Degree by Research Supervision (University of Adelaide)

    Date Role Research Topic Program Degree Type Student Load Student Name
    2023 Principal Supervisor Study of bacteriophage protein structures for the production of improved antimicrobial agents Master of Philosophy Master Full Time Ms Sarah Jayne Eisemann
    2023 Co-Supervisor Characterisation of the biochemical and functional phenotype of the brain and primary neuronal cultures to further understand the neuropathology in a childhood inherited neurodegenerative disorder. Doctor of Philosophy Doctorate Part Time Miss Kleopatra Pericleous
    2022 Principal Supervisor Engineering small molecule binding proteins as novel biosensors Doctor of Philosophy Doctorate Full Time Mr Alix Charles Harlington
    2021 Principal Supervisor Engineering biosensors for wine spoilage Doctor of Philosophy Doctorate Full Time Mr Ranjith Manjula Meemanage Cebreco
  • Past Higher Degree by Research Supervision (University of Adelaide)

    Date Role Research Topic Program Degree Type Student Load Student Name
    2019 - 2023 Co-Supervisor Protein and Reaction Engineering of P450 Enzymes for Selective Oxidations Doctor of Philosophy Doctorate Full Time Dr Joel Hoong Zhang Lee
    2018 - 2021 Co-Supervisor Structural and Biochemical Insights into Antifungal Drug Targets from Aspergillus fumigatus Doctor of Philosophy Doctorate Full Time Ms Stephanie Nguyen
    2018 - 2023 Co-Supervisor Functional and Structural Characterisation of Bacterial ATP-grasp Ligases Doctor of Philosophy Doctorate Full Time Mr Jordan Luke Pederick
    2018 - 2024 Principal Supervisor Development of the PHEARLESS system and its application for directed protein mutagenesis and characterisation of putative endolysin activity Doctor of Philosophy Doctorate Full Time Miss Hannah Rose Bonham
    2017 - 2021 Principal Supervisor Investigating catalytically inactive Cas proteins as transcriptional roadblocks Doctor of Philosophy Doctorate Full Time Miss Alana Jane Donnelly
    2017 - 2020 Principal Supervisor Bacteriophage 186 Investigating the role of transcriptional regulators CI, Apl, CII and Tum at the lytic/lysogenic switch during 186 prophage induction Doctor of Philosophy Doctorate Full Time Miss Alejandra Isabel
    2015 - 2021 Principal Supervisor Structural Characterization of Lysogeny-Promoting Transcription Factor of Bacteriophage 186 Doctor of Philosophy Doctorate Full Time Mr Jia Quyen Truong
    2011 - 2014 Principal Supervisor Testing the DNA loop domain model in Escherichia coli Doctor of Philosophy Doctorate Full Time Mr David Priest
    2010 - 2014 Principal Supervisor DNA looping mediated transcriptional regulation Doctor of Philosophy Doctorate Full Time Mr Lun Cui
    2008 - 2015 Principal Supervisor The Design, Synthesis and Quantitative Analysis of a Bistable Mixed Feedback Loop Gene Network Doctor of Philosophy Doctorate Full Time Mr Julian Pietsch
    2006 - 2008 Co-Supervisor Calcium and Phosphoinositides Regulations in Alpha-Actinin-4 F-Actin Binding Doctor of Philosophy Doctorate Full Time Mr Huang-Hui Chen
  • Mentoring

    Date Topic Location Name
    2018 - ongoing Synthetic Biology The University of Adelaide Dr. Fiona Whelan
    2012 - ongoing DNA looping, Synthetic Biology The University of Adelaide Dr. Andrew Hao
    2009 - 2016 Phage genetics, synthetic biology The University of Adelaide Dr. Iain Murchland
    2007 - 2012 Post-doctoral fellow The University of Adelaide Dr. Alexandra Ahlgren-Berg
    2005 - 2007 Post-doctoral Fellow The University of Adelaide Dr. Rachel Schubert
  • Committee Memberships

    Date Role Committee Institution Country
    2017 - ongoing Chair Associate Head (HDR) The University of Adelaide Australia
    2017 - ongoing Member Faculty of Science Higher Degree by Research The University of Adelaide Australia
    2017 - ongoing Member Postgraduate Coordinator The University of Adelaide Australia
    2015 - ongoing Member School of Biological Sciences Executive The University of Adelaide Australia
    2007 - ongoing Convener School Summer Scholarship Coordinator University of Adelaide Australia
  • Memberships

    Date Role Membership Country
    2015 - ongoing Representative Synthetic Biology Australasia Australia
    1993 - ongoing Member Australian Society for Biochemistry and Molecular Biology Australia
  • Editorial Boards

    Date Role Editorial Board Name Institution Country
    2020 - ongoing Associate Editor Biophysical Reviews The University of Adelaide Australia
  • Review, Assessment, Editorial and Advice

    Date Title Type Institution Country
    2019 - ongoing Associate Editor - Biophysical Reviews Editorial The Univeristy of Adelaide Australia
  • Position: Associate Professor/Reader
  • Phone: 83135361
  • Email: keith.shearwin@adelaide.edu.au
  • Fax: 83134362
  • Campus: North Terrace
  • Building: Molecular Life Sciences, floor 2
  • Org Unit: Molecular and Biomedical Science

Connect With Me
External Profiles