
Dr Ian Dodd
Biochemistry Research Officer
School of Biological Sciences
Faculty of Sciences, Engineering and Technology
Eligible to supervise Masters and PhD - email supervisor to discuss availability.
I am based in the laboratory of Assoc Prof Keith Shearwin (Biochemistry, Molecular and Biomedical Science) https://researchers.adelaide.edu.au/profile/keith.shearwin.
Research in the Shearwin lab integrates biochemistry, genetics and mathematical modelling to characterise fundamental mechanisms of gene control and how these mechanism are combined to create gene regulatory circuits with complex functions. 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.
The phage systems have been the springboard for my particular interests in DNA looping, molecular traffic on DNA and epigenetics.
DNA loops are created when proteins bound to separated sites on the same DNA interact with each other. These interactions can be critical in gene regulation (for example between eukaryotic promoters and enhancers), but it is still not understood how these loops can form efficiently, especially over long distances, and how certain looping interactions are chosen over others. Our research utilizes experiments with well-defined looping proteins in E. coli and mathematical modelling to find simple rules that govern looping efficiency and how this is affected by the positive or negative interactions between different DNA loops.
A simple picture of the transcription of a gene has RNA polymerase binding to the DNA at the promoter, initiating transcription and then transcribing uneventfully until reaching a terminator sequence and falling off the DNA. However, in reality the DNA is not a ‘freeway’ for RNA polymerase but is more like a crowded one-lane two-way street. As an RNA polymerase makes its way along the DNA, its progress can be affected by a myriad of ‘roadblock’ proteins bound to the DNA and also by other traffic such as RNA polymerases moving in the opposite direction. How can efficient transcription occur under such conditions? How are these obstacles used by the cell to regulate transcription? How is the function of the DNA-bound proteins affected by the passage of RNA polymerase? We examine these questions using synthetic gene expression constructs in E. coli cells and mathematical modelling.
Epigenetics allows cells with the same genome and that share the same environment to exist in distinct, persistent and heritable gene expression states. During development, cells with different identities are created by transient environmental signals causing changes in gene expression that persist after the signal disappears and are passed to the cell’s descendants. This epigenetic cell differentiation is needed to produce the many diffeent specialized cells required in multicellular organisms. Such stable and heritable alternative gene expression states can be generated by positive feedback in circuits of diffusible gene regulators. We study how the phage 186 and lambda regulatory proteins are wired to create bistable circuits and how this affects the choice between lytic and lysogenic development. We also design and test synthetic bistable circuits made from these phage components. The other major class of epigenetic mechanism is chromatin-based, where gene expression is regulated by self-sustaining modifications to chromatin, such as histone modifications or DNA methylation. My work in this area is solely theoretical, and is a collaboration with Prof Kim Sneppen, a physicist at the Niels Bohr Institute in Copenhagen. We mathematically model positive feedback, where nucleosomes carrying a particular modification stimulate formation of the same modification on nearby nucleosomes, or methylated CpG DNA sequences stimulate methylation of nearby CpGs. Our work demonstrates the need for this positive feedback to be ultrasensitive (cooperative) and to act beyond nearest neighbours (not a simple spreading), in order to generate distinct, stable and heritable states.
I am based in the laboratory of Assoc Prof Keith Shearwin (Biochemistry, Molecular and Biomedical Science) https://researchers.adelaide.edu.au/profile/keith.shearwin.
Research in the Shearwin lab integrates biochemistry, genetics and mathematical modelling to characterise fundamental mechanisms of gene control and how these mechanism are combined to create gene regulatory circuits with complex functions. 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.
The phage systems have been the springboard for my particular interests in DNA looping, molecular traffic on DNA and epigenetics.
DNA loops are created when proteins bound to separated sites on the same DNA interact with each other. These interactions can be critical in gene regulation (for example between eukaryotic promoters and enhancers), but it is still not understood how these loops can form efficiently, especially over long distances, and how certain looping interactions are chosen over others. Our research utilizes experiments with well-defined looping proteins in E. coli and mathematical modelling to find simple rules that govern looping efficiency and how this is affected by the positive or negative interactions between different DNA loops.
A simple picture of the transcription of a gene has RNA polymerase binding to the DNA at the promoter, initiating transcription and then transcribing uneventfully until reaching a terminator sequence and falling off the DNA. However, in reality the DNA is not a ‘freeway’ for RNA polymerase but is more like a crowded one-lane two-way street. As an RNA polymerase makes its way along the DNA, its progress can be affected by a myriad of ‘roadblock’ proteins bound to the DNA and also by other traffic such as RNA polymerases moving in the opposite direction. How can efficient transcription occur under such conditions? How are these obstacles used by the cell to regulate transcription? How is the function of the DNA-bound proteins affected by the passage of RNA polymerase? We examine these questions using synthetic gene expression constructs in E. coli cells and mathematical modelling.
Epigenetics allows cells with the same genome and that share the same environment to exist in distinct, persistent and heritable gene expression states. During development, cells with different identities are created by transient environmental signals causing changes in gene expression that persist after the signal disappears and are passed to the cell’s descendants. This epigenetic cell differentiation is needed to produce the many diffeent specialized cells required in multicellular organisms. Such stable and heritable alternative gene expression states can be generated by positive feedback in circuits of diffusible gene regulators. We study how the phage 186 and lambda regulatory proteins are wired to create bistable circuits and how this affects the choice between lytic and lysogenic development. We also design and test synthetic bistable circuits made from these phage components. The other major class of epigenetic mechanism is chromatin-based, where gene expression is regulated by self-sustaining modifications to chromatin, such as histone modifications or DNA methylation. My work in this area is solely theoretical, and is a collaboration with Prof Kim Sneppen, a physicist at the Niels Bohr Institute in Copenhagen. We mathematically model positive feedback, where nucleosomes carrying a particular modification stimulate formation of the same modification on nearby nucleosomes, or methylated CpG DNA sequences stimulate methylation of nearby CpGs. Our work demonstrates the need for this positive feedback to be ultrasensitive (cooperative) and to act beyond nearest neighbours (not a simple spreading), in order to generate distinct, stable and heritable states.
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Appointments
Date Position Institution name 1992 - 2018 Postdoctoral researcher University of Adelaide -
Education
Date Institution name Country Title 1982 - 1992 University of Adelaide Australia PhD 1976 - 1981 University of Adelaide Australia B.Sc (Hons) -
Research Interests
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Journals
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Book Chapters
Year Citation 2017 Dodd, I., & Sneppen, K. (2017). Modeling Bistable Chromatin States. In L. Ringrose (Ed.), Epigenetics and Systems Biology (pp. 145-168). London, UK: Elsevier.
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Conference Items
Year Citation 2017 Hao, N., Shearwin, K., & Dodd, I. (2017). Understanding and Manipulating Chromosomal-Scale DNA Looping in Escherichia coli. Poster session presented at the meeting of 2017 Synthetic Biology: Engineering, Evolution & Design (SEED) : Proceedings. Vancouver, Canada. 2017 Hao, N., Priest, D., Dodd, I., & Shearwin, K. (2017). Programmable DNA looping in vivo. Poster session presented at the meeting of Australia-China Symposium on Synthetic Biology. Brisbane. 2016 Hao, N., Shearwin, K., & Dodd, I. (2016). Road Rules for Traffic on DNA: Gene Regulation by Encounters between Transcribing RNA Polymerases and DNA-bound Proteins. Poster session presented at the meeting of Synthetic Biology: Engineering, Evolution & Design (SEED). Chicago, USA. 2016 Hao, N., Shearwin, K., & Dodd, I. (2016). Understand DNA looping in vivo - a synthetic biology approach. Poster session presented at the meeting of OCE Cutting Edge Conference in Synthetic Biology. Canberra. 2015 Hao, N., Krishna, S., Shearwin, K., & Dodd, I. (2015). Road Rules for Traffic on DNA: Gene Regulation by Encounters between Transcribing RNA Polymerases and DNA-bound Proteins. Poster session presented at the meeting of 2nd International Synthetic & Systems Biology Summer School. Taormina - Sicily, Italy. 2015 Kumar, S., Priest, D. G., Yan, Y., Dodd, I. B., Shearwin, K. E., & Dunlap, D. D. (2015). Estimation of DNA Loop Interactions Supports the Loop Domain Model of Insulator Action. Poster session presented at the meeting of BIOPHYSICAL JOURNAL. CELL PRESS.
2014 Shearwin, K., Cui, L., Murchland, I., & Dodd, I. B. (2014). Long-range DNA looping in the lambda genetic switch. Poster session presented at the meeting of Abstracts of the 58th Annual Meeting of the Biophysical Society, as published in Biophysical Journal. San Francisco, CA: Cell Press.
2012 Wang, H., Dodd, I. B., Keith, S., Dunlap, D., & Finzi, L. (2012). Automated DNA Tracing on AFM Images Helps the Study of 186 Repressor-DNA Interactions. Poster session presented at the meeting of BIOPHYSICAL JOURNAL. San Diego, CA: CELL PRESS.
2012 Hao, N., Shearwin, K., Dodd, I., Whitelaw, M., & Chapman-Smith, A. (2012). Reverse Bacterial Two Hybrid: A New Tool for Studying Dimeric Protein Interactions. Poster session presented at the meeting of ASBMB ComBio conference. Adelaide. 2010 Wang, H., Dodd, I. B., Shearwin, K., Dunlap, D., & Finzi, L. (2010). Coliphage 186 genetic switch: a single molecule study. Poster session presented at the meeting of Meeting Abstracts. Biophysical Journal. San Francisco: Cell Press.
2009 Hao, N., Shearwin., Dodd, I., Whitelaw, M., & Chapman-Smith, A. (2009). Reverse Bacterial two Hybrid (RevB2H) method for studying protein-protein interactions. Poster session presented at the meeting of Network in Genes and Environment in Development (NGED) Forum. Palm Cove, Queensland. 2009 Hao, N., Shearwin, K., Dodd, I., Whitelaw, M., & Chapman-smith, A. (2009). A novel Reverse Bacterial two Hybrid (RevB2H) method for studying protein-protein interactions and screening for potential therapeutics. Poster session presented at the meeting of Australian Society for Medical Research (ASMR) SA Scientific Meeting. Adelaide.
- 2016
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1100651 - Understanding and manipulating long-range DNA looping in gene regulation (Grant in RM)
- 2015
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Rational design of genetic circuits that respond to transient signals (Grant in RM)
- 2012
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Mechanisms of propagation and containment of gene silencing (Grant in RM)
- 2011
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Road rules for traffic on DNA - gene regulation by encounters between transcribing RNA polymerases and DNA-bound proteins (Grant in RM)
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The rational design and construction of new genetic circuits for use in synthetic biology (Grant in RM)
- 2010
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Understanding and controlling PAS domain interactions in basic helix-loop-helix transcription factors (Grant in RM)
- 2006
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Transcriptional interference in gene regulatory decisions (Grant in RM)
- 1997
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Stability in a transcriptional switch: repression despite passing transcription (Grant in RM)
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Current Higher Degree by Research Supervision (University of Adelaide)
Date Role Research Topic Program Degree Type Student Load Student Name 2019 Co-Supervisor Bacteriophage based applications in synthetic biology Doctor of Philosophy Doctorate Full Time Lawrence Daniel Beltrame -
Past Higher Degree by Research Supervision (University of Adelaide)
Date Role Research Topic Program Degree Type Student Load Student Name 2017 - 2021 Co-Supervisor Investigating catalytically inactive Cas proteins as transcriptional roadblocks Doctor of Philosophy Doctorate Full Time Miss Alana Jane Donnelly 2017 - 2020 Co-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 Co-Supervisor Structural Characterization of Lysogeny-Promoting Transcription Factor of Bacteriophage 186 Doctor of Philosophy Doctorate Full Time Mr Jia Quyen Truong 2011 - 2014 Co-Supervisor Testing the DNA loop domain model in Escherichia coli Doctor of Philosophy Doctorate Full Time Mr David Priest 2010 - 2014 Co-Supervisor DNA looping mediated transcriptional regulation Doctor of Philosophy Doctorate Full Time Mr Lun Cui 2008 - 2015 Co-Supervisor The Design, Synthesis and Quantitative Analysis of a Bistable Mixed Feedback Loop Gene Network Doctor of Philosophy Doctorate Full Time Mr Julian Pietsch
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