Australian Institute for Bioengineering and Nanotechnology
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Professor Lars Nielsen is leading the development of experimental and computational tools to analyse and design complex biological systems. His expertise in metabolic modelling and flux analysis is available nowhere else in Australia – and in few labs across the world. Professor Nielsen’s studies of biological systems as diverse as bacteria, baker's yeast, sugarcane, insects and mammals has attracted industrial partnerships with companies including Dow, Metabolix, Amyris, LanzaTech, Boeing, Virgin Australia and GE. These metabolic engineering partnerships have focussed on developing new ways of producing aviation fuel, various materials and bioactives (antibiotics, biopesticides, monoclonal antibodies). Professor Nielsen is also applying system analysis and design approaches to tissue engineering including novel strategies for generating microtissues for drug screening and using stem cells to produce red and white blood cells for transfusion.
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Professor Nielsen collaborates with some of the world’s pre-eminent metabolic engineers. A joint project with Prof Sang Yup Lee (KAIST, Korea) enabled several extended mutual visits to explore use of sugar for higher value products. A separate project focused on producing synthetic aviation fuel based on isoprenoids involves Professor Nielsen collaborating with global synthetic biotechnology company Amyris and leading isoprenoid metabolic engineer Professor Jay Keasling, from UC Berkeley. Professor Nielsen has secured $8million since 2006 from industry through research grants with US, European, Japanese, Korean, New Zealand and Australian companies.
Dr Marloes Dekker Nitert is an Associate Professor at The University of Queensland. Marloes is a biomedical researcher with a PhD from Lund University in Sweden. Her research focuses on the role of metabolism in complications of pregnancy. She currently heads a laboratory research group at the School of Chemistry and Molecular Biosciences studying the role of metabolism in pregnancy complications and especially how the gut microbiome contributes to a healthy pregnancy and to pregnancy complications. Marloes works closely together with clinician-scientists and clinicians at the Royal Brisbane and Women’s Hospital and the Mater Mothers' Hospital to do her translational research. Marloes is a board member of the Australian Society for Medical Research and a past Council member of the Society of Obstetric Medicine Australia and New Zealand.
Michael Noad graduated with a Bachelor of Veterinary Science from UQ in 1990. After working primarily as a small animal vet in Queensland and the UK, Mike returned to Australia to undertake a PhD in humpback whale acoustic behaviour at the University of Sydney in 1995. In 2002, after finishing his PhD, Mike became a postdoctoral fellow in the School of Integraitve Biology at UQ. In 2003 he was employed as a lecturer in the School of Veterinary Science. He is currently a professor at UQ, dividing his time between veterinary science, where he teaches anatomy, and marine science, the focus of his research. In 2019 he became the Academic Director of the Moreton Bay Research Station, and in 2022 the Director of the Centre for Marine Science while still retaining a substantive apointment in the School of Veterinary Science.
Research:
The key areas of Mike's research are the effects of anthopogenic underwater noise on whales, the evolution and function of humpback whale song, social learning and culture in animals, and marine mammal population ecology. With regards to the effects of anthropogenic underwater noise on whales, there is currently a great deal of concern about how anthropogenic noise such as military sonar, oil and gas exploration activity and commercial shipping traffic, may adversely affect marine mammals. Mike has been involved in several large collaborative projects in this area, the largest being BRAHSS where the team studied the behavioural changes of humpback whales in response to powerful seismic airguns. His work on the evolution and function of humpback whale song is focused on how the animals themselves use sound to communicate. The songs of these whales is one of the most complex acoustic displays of any animal known. The songs are not static, but constantly change, and although the songs are almost certainly used as a sexual signal, the changing nature of the song makes understanding how this works challenging. His work on social learning and culture in animals also involves humpback whale songs, but focuses on how the whales learn the songs from each other, both within and between populations. As the patterns are usually unique to a population but can be transmitted over time to other populations, humpback song is the most extreme example of a vocal cultural trait in any species as well as an excellent model for studying social learning, the process whereby the whales perceive and learn new songs. Mike's last research area is marine mammal population ecology, and the primary project is the population ecology of the east Australian humpback whales. This population was almost completely extirpated in the early 1960s through hunting, but has since undergone a rapid recovery. Its long term trajectory, however, is uncertain due to a number of factors including possibly overshooting the natural carrying capacity of the population, and climate change.
Affiliate of ARC COE for Innovations in Peptide and Protein Science
ARC COE for Innovations in Peptide and Protein Science
Institute for Molecular Bioscience
Affiliate Professor of School of Chemistry and Molecular Biosciences
School of Chemistry and Molecular Biosciences
Faculty of Science
Professorial Research Fellow and Group Leader
Australian Institute for Bioengineering and Nanotechnology
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Megan O’Mara is a Professor and Group Leader at the Australian Institute for Bioengineering and Nanotechnology (AIBN), UQ. Her group uses multiscale modelling techniques to understand how changes in the biochemical environment of the cell membranes alters membrane properties and modulates the function of membrane proteins. She has research interests in multidrug resistance, computational drug design and delivery, biopolymers, and personalized medicine. Megan completed her PhD in biophysics at the Australian National University in 2005 before moving to the University of Calgary, Canada, to take up a Canadian Institutes of Health Research Postdoctoral Fellowship. In 2009, she returned to Australia to join University of Queensland’s School of Chemistry and Molecular Biosciences as a UQ Postdoctoral Fellow, before commencing an ARC DECRA in 2012 where she continued her computational work on membrane protein dynamics. In 2015, Megan joined the Research School of Chemistry, Australian National University in 2015 as Rita Cornforth Fellow and Senior Lecturer. In 2019 she was promoted to Associate Professor and was Associate Director (Education) of the Research School of Chemistry ANU in 2019-2021. In April 2022 she relocated to AIBN.
Affiliate of Centre for Extracellular Vesicle Nanomedicine
Centre for Extracellular Vesicle Nanomedicine
Faculty of Health, Medicine and Behavioural Sciences
NHMRC Leadership Fellow
UQ Centre for Clinical Research
Faculty of Health, Medicine and Behavioural Sciences
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Professor Obermair is the Director of Queensland Centre for Gynaecological Cancer Research (QCGC Research). He is a Professor of Gynaecological Oncology since 2007, a Senior Medical Officer at Royal Brisbane & Women’s Hospital and a Visiting Medical Officer at St Andrews War Memorial Hospital and Buderim Private Hospital. He holds an Honorary title of Professor at UQ since 2006.
Professor Obermair is an internationally recognised leader in gynaecological oncology research and treatment and has lead the research team at QCGC Research since establishing it in 2003.
I studied Technical Mathematics at the Vienna University of Technology. I also earned a Master's degree in Law and I finished the first ("non-clinical") part of Medical Studies at the University of Vienna. I earned my PhD in Applied Mathematics at the University of Vienna in 2007. My PhD advisor was Christian Schmeiser, my co-advisor was Peter Markowich. I spent several months at the University of Buenos Aires working with C. Lederman and at the ENS-Paris rue d'Ulm in the group of B. Perthame.
Before coming to UQ, I held post-doc positions at the Wolfgang Pauli Insitute (Vienna), University of Vienna and the Austrian Academy of Sciences (RICAM). In 2013 I won an Erwin Schrödinger Fellowship of the Austrian Science Fund (FWF). I was a post-doc researcher in the group of Alex Mogilner first at UC Davis, then at the Courant Institute of Math. Sciences (New York University).
Dr. Melanie Oey is currently Research Officer at the Institute for Molecular Bioscience in the Group of Prof. Ben Hankamer. She was born in Berlin, Germany, and went to the University of Potsdam to study Biochemistry. During her studies she worked at the Max-Planck Institute of Molecular Plant Physiology in Golm, Germany, where she also received her Ph.D. in 2009 for her work on the production of lysin antibiotics in tobacco plants. In the same year she came to Australia to work at the University of Queensland, and has since then developed new technologies which are base for the newly launched "Breakthrough Science Program in Algal Biomedicine" at the Institute for Molecular Bioscience.
Her research interestes are:
- High value product production (e.g. vaccines, antibiotics, pain killer) in Algae via chloroplast and nuclear transformation
- Improvement of bio-hydrogen production from microalgae
- Development of new molecular tools for microalgae
Her work has been funded by the Australian Research Council (ARC), the National Health and Medical Research Council (NHMRC) and the German Academic Exchange Service (DAAD).
Queensland Alliance for Agriculture and Food Innovation
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Dr. Ong is an exceptional and driven researcher in the field of Animal Health, and her work revolves around studying pathogen genomes, transcriptomes, and host-associated metagenomes to enhance animals' resistance to diseases and improve their overall health and productivity.
One remarkable aspect of Dr. Ong's expertise is her versatility and enthusiasm for both wet lab and dry lab (bioinformatics) work. She finds equal joy in conducting hands-on experiments in the wet lab and diving into data analysis and computational work in the bioinformatics domain. This multidisciplinary approach empowers her to gain comprehensive insights into her research subjects and tackle complex challenges from various angles. Dr. Ong's vast skillset encompasses molecular biology and expertise in utilizing 2nd and 3rd generation sequencing technologies, along with her proficiency in bioinformatics tools and techniques. This diverse knowledge allows her to explore and employ cutting-edge methodologies, providing her with a unique advantage in her research endeavors.
One of Dr. Ong's significant achievements was conducting the first cattle reproductive tract metagenomic study in Australia. This groundbreaking study likely contributed valuable information about the reproductive health of cattle and opened new avenues for further research in this area. Additionally, her contributions extend to the assembly of complete genomes for multiple pathogens, such as Campylobacter fetus and Bovicola ovis. This accomplishment is instrumental in understanding these pathogens' genetic makeup, evolution, and mechanisms of infection, which is vital in developing targeted strategies to combat diseases affecting animals.
In The Ortiz-Barrientos Lab we seek to understand how natural selection drives the origin of traits and new species. We combine empirical and theoretical approaches from across multiple disciplines.
We are located in beautiful Brisbane, Australia, in the School of The Environment at The University of Queensland.
Please explore our pages to learn about research, culture, and the team of scientists that bring their passion and creativity to discovering how nature works.
Affiliate Professor of School of Biomedical Sciences
School of Biomedical Sciences
Faculty of Health, Medicine and Behavioural Sciences
Affiliate of Centre for Cardiovascular Health and Research
Centre for Cardiovascular Health and Research
Faculty of Health, Medicine and Behavioural Sciences
Affiliate of The Centre for Cell Biology of Chronic Disease
Centre for Cell Biology of Chronic Disease
Institute for Molecular Bioscience
National Heart Foundation of Australia Future Leader Fellow - Group Leader
Institute for Molecular Bioscience
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Career Summary: 2009: PhD, University of Michigan, USA with training in cardiac physiology, modelling myocardial ischemia in vivo and in vitro, and development of therapeutic approaches for myocardial ischemia; 2009–2015: Postdoctoral Research Fellow, University of Washington, Institute for Stem Cell and Regenerative Medicine, USA with training in stem cell biology, genomics, genome editing, and cell therapeutics for ischemic heart disease; 2015–current: Group Leader, University of Queensland (UQ), Institute for Molecular Bioscience; 2022-current: Associate Professor, UQ; 2018–2021 and 2023-2026: National Heart Foundation Future Leader Fellow. Dr. Palpant’s research team has expertise in human stem cell biology, computational genomics, and cardiac physiology, which enables them to translate outcomes from cell biology and genomics to disease modelling, drug discovery, and preclinical modelling.
Faculty of Health, Medicine and Behavioural Sciences
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Marie-Odile Parat (MO) joined the School of Pharmacy as Senior Lecturer in December 2007.
MO obtained her Pharm.D. from University Joseph Fourier in Grenoble, France, a Masters in Cutaneous Biology from University Claude Bernard in Lyon, France and her Ph.D. in Cell Biology from University Joseph Fourier in Grenoble, France. She further has post graduate diplomas in the fields of Biomedical and Industrial Pharmacy, Photobiology, Pharmaceutical Management, and Public Health.
MO did her Pharmaceutical Residency at the University Hospitals of Grenoble, France in the Sterile Pharmaceutical Supplies Headquarters, the Department of Nuclear Medicine, and the Laboratory Medicine Department of Biochemistry. Attracted by international working experience, she carried out research within the R&D laboratories of Estee Lauder in Melville, NY. She further worked for the United Nations International Trade center in Geneva, Switzerland, where she was the Product Specialist on market information for pharmaceutical raw materials/essential drugs for three years in collaboration with the World Health Organization.
She later performed post-doctoral research in the Universidade de São Paulo, SP, Brasil and The Cleveland Clinic Foundation in the United States. She was appointed as a Staff Scientist in the Center for Anesthesiology Research of the Cleveland Clinic in 2003, an Assistant Professor of Molecular Medicine in the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, and a Member of the Case Cancer Center.
During her research career MO has attracted awards from various funding agencies including the Research Funding Agency of the State of São Paulo (FAPESP), the American Heart Association, the Ohio Cancer Research Associates, the American Cancer Society, the National Heart Foundation of Australia, Cancer Council Queensland, Australian and New Zealand College of Anaesthetists and the Australia Research Council (ARC).
The long term goal of the Parat laboratory is to provide insight for novel cancer therapies. A basic science team focusses on endothelial and cancer cell migration, invasion, angiogenesis, and specialized plasma membrane subdomains termed caveolae. A translational axis of research evaluates novel mechanisms by which opioids administered to cancer patients modulate the risk of long term tumour recurrence and metastasis.
I am a molecular virologist and postdoctoral research fellow in Prof. Alexander Khromykh's laboratory, specialising in virus evolution, virus bioinformatics, and reverse genetics.
My research journey began with a Bachelor of Science, First Class Honours in Molecular Biology from The University of Queensland (2015). I then pursued my PhD (2016-2021) at UQ's School of Biology under Prof. Sassan Asgari, where I analysed the virome and microbiome of Aedes aegypti and Aedes albopictus mosquitoes, focusing on their interactions with Wolbachia pipientis infections.
Since 2021, I have been a postdoctoral researcher in Prof. Alexander Khromykh's RNA Virology lab. Here, I contributed to developing the SARS-CoV-2 circular polymerase extension reaction (CPER) reverse-genetics methodology. As a physical containment 3 (PC3) researcher, I examine the virological properties of Flaviviruses and SARS-CoV-2 viruses under stringent PC3 conditions. Recently, with support from Therapeutic Innovation Australia and the Australian Infectious Diseases Research Centre, I have been utilising the Kunjin virus replicon system as a versatile and durable self-replicating RNA platform for vaccine and protein replacement therapy.
Beyond my virology work, I actively provide bioinformatics and phylogenetics support within UQ and internationally. Let's connect if you’re interested in collaborating on differential gene and ncRNA expression analysis, ATAC-sequencing, ancestral state prediction, virus discovery, or microbiome analyses.
I am also on the organising committee of MicroSeq (2023-2024), an Australasian Microbiology conference focused on microbial sequencing promoting PhD students and early career researchers. Additionally, I am an incoming Ex Officio member of the Australian Society for Microbiology (ASM) Queensland branch.
Affiliate of The Centre for Cell Biology of Chronic Disease
Centre for Cell Biology of Chronic Disease
Institute for Molecular Bioscience
ARC Laureate Fellow - Group Leader
Institute for Molecular Bioscience
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Our research focuses on understanding how cells work and what goes wrong in disease. We are studying the role of cellular organelles in defence against pathogens, the molecular changes underlying muscle disease, and optimising methods to deliver therapeutics to specific cell types in whole animals.
Professor Robert Parton is an ARC Laureate Fellow, a group leader in the IMB Centre for Cell Biology of Chronic Disease, and Deputy Director of the Centre for Microscopy and Microanalysis. He is a Fellow of the Australian Academy of Science and an Associate Member of EMBO.
Faculty of Health, Medicine and Behavioural Sciences
Adjunct Senior Fellow
School of Public Health
Faculty of Health, Medicine and Behavioural Sciences
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Dr Brad Partridge has been a researcher in hospitals and universities for almost 20 years. His work has covered ethical, social, and policy issues related to a range of topics in healthcare including addiction, concussion management, psychiatry, midwifery, and biomedical enhancement technologies. He has written about conflicts of interest, medicalisation, and stakeholder attitudes towards models of treatment, and has extensive experience using qualitative research methods.
Brad joined the UQ Business School in April 2023 where he is exploring trust, and the attitudes of clinicians, towards incorporating Artificial Intelligence (AI) tools into the clinical decision-making process for melanoma detection, as part of an NHMRC Synergy Grant.
Brad was previously a postdoctoral research fellow in biomedical ethics at Mayo Clinic (Minnesota, USA), and was a visiting research fellow with the Neuroethics Research Group at the Montreal Clinical Research Institute (IRCM), in Canada. From 2011-2014 he was an NHMRC postdoctoral fellow with the addiction neuroethics group led by Prof. Wayne Hall at the University of Queensland Centre for Clinical Research (UQCCR). There, he was a Chief Investigator on two ARC Discovery Grants related to 1) the non-medical use of prescription stimulants, and 2) the ethical, social and policy implications of neurobiological explanations of addiction. Between 2015-2023 he held research in public hospitals within Metro-North Hospital and Health Service (Queensland Health), and at the Queensland Centre for Mental Health Research (QCMHR).
Brad’s PhD was from the University of Queensland School of Public Health. He also has a Master of Arts in Philosophy, and Bachelor of Psychology (Hons) from the University of New England.
Affiliate of ARC COE for the Digital Child (UQ Node)
ARC COE for the Digital Child
Faculty of Humanities, Arts and Social Sciences
Affiliate of ARC COE for Children and Families Over the Lifecourse
ARC COE for Children and Families Over the Lifecourse
Faculty of Humanities, Arts and Social Sciences
Senior Research Fellow
Child Health Research Centre
Faculty of Health, Medicine and Behavioural Sciences
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Dr Cassandra Pattinson research centres around exploring the effects of sleep and circadian rhythms on health, wellbeing, and recovery across the lifespan. Dr Pattinson is a Senior Research Fellow at the Child Health Research Centre (CHRC) and the ARC centre of Excellence for the Digital Child. The Digital Child aims to support children growing up in the rapidly changing digital world, and provide strong evidence and guidance for children, families, educators, government and other concerned with children’s wellbeing. Her work has been supported by the ARC (including recently awarded an ARC Discovery Early Career Award, 2025), NHMRC, NIH and the DSTG, as well as the Australian Federal Government and Queensland Government.
Her research has involved a range of populations from children and adolescents, through to military personnel and athletes. Dr Pattinson's research spans a range of study designs and methodologies, including longitudinal studies tracking large child cohorts (>2000 children), standard observation techniques, survey and individualised standard child assessment, as well as studies employing physiological (actigraphy, spectrometry) and biological (hormones, proteomic, genomic) designs. Dr Pattinson also has a strong track record in research translation, these have included manuscripts in top scientific journals, reports for government and non-government organisations, development of professional development programs, as well as designing and presenting vodcasts and resources (e.g. fact sheets, workshops) to parent groups, young adults, government departments and the early childhood sector.
At CHRC Dr Pattinson is a part of the Community Sleep Health Group. This group collaborates with many other groups around broader issues of sleep and technology, sleep and the environment (including disasters), mental health and wellbeing, pain, disability, and new technologies and approaches.
My research interests have concentrated on the molecular genetic analysis of multigene phenotypes of bacteria encompassing pathogenicity, bacterial degradation of synthetic environmental pollutants, photosynthesis and the synthesis of antitumour antibiotics. My PhD research focussed on plasmids and mapping of the genome of the human pathogen P. aeruginosa (Pemberton,and Holloway, 1972a; Pemberton,and Holloway,1972b;Pemberton and Holloway,1973). I continued this research as a postdoc at UC Berkeley with John Clark in the Department of Molecular Biology in the Wendell Stanley Virus laboratory. I am grateful to Mark Guyer who taught me how to isolate large plasmid DNAs. In Robley Williams lab I learnt how to use the Kleinschmidt and Zahn technique for spreading the plasmid DNA on an electronmicroscope grid and metal shadow the sample to visualise it under an electron microscope; I am grateful to Robley Williams for showing me how to metal shadow my samples (Pemberton,1973; Pemberton and AJ Clark,1973; Miller, Pemberton and Richards,1974;Pemberton,1974;Miller,Pemberton and Clark,1977). After advice from John Clark and when I returned to Australia and took up an appointment with UQ I decided to diversify my research. During my postdoc I worked alongside Anne Emerick who was working with the CAM (camphor degradation) plasmid. John Clark put me on her advisory panel (alongside Mike Doudoroff and Norberto Palleroni) making her my first PhD student. The bacterial degradation of such complex naturally occurring molecules such as camphor required a large number of steps requiring a large number of genes hence a large plasmid. I decided to determine if soil bacteria had evolved plasmids which encoded the degradation of man-made molecules. I chose the synthetic herbicide 2,4-D. My research was the first to identify, isolate and clone genes responsible for the degradation of a man-made molecule –moreover the 2,4-D degradation was encoded by a broad host range plasmid, providing an explanation of how microorganisms rapidly evolve the ability to degrade and recycle a vast array of worldwide synthetic environmental pollutants which cause a range of diseases from cancer to birth defects (Pemberton & Fisher, Nature, 1977). One of the most widely studied microorganisms is the bacterium Ralstonia eutropha JMP134 pJP4 (Hgr) which has an extraordinary ability to degrade and recycle the most complex and most toxic synthetic molecules (Don and Pemberton, J.Bacteriol, 1981;Schmidt et.al.,2011. Catabolic Plasmids.Encyclopedia of Life Sciences). Famously more recent studies have shown that there are genes and gene clusters encoding the degradation of plastics, explosives and chemical weapons of war . Detailed studies of bacterial genes involved in the environmental degradation and recycling of a wide range naturally occurring and synthetic molecules show that degradation genes and degradation gene clusters play a major role in the worldwide carbon cycle.
Photosynthesis is considered the most important biological process on earth. And one of the most intensively studied photosynthetic organisms is the bacterium Rhodobacter sphaeroides. To start the research a local strain of R.sphaeroides, designated RS601, was isolated by Bill Tucker (my first australian PhD student) from a water sample obtained from a roadside ditch in Brisbane (Pemberton and Tucker,1977;Tucker and Pemberton,1978;1979;1980). One of the first discoveries made with this strain was lysogenic conversion to antibiotic resistance by a naturally occurring virus .(JM Pemberton, WT Tucker - Nature, 1977).
Subsequently when this strain was infected withe the broad host plasmid RP1 carrying the mecuric ion transposon Tn501 chromosome transfer occurred. This allowed the construction of the first genetic map of a photosynthetic bacterium(Pemberton and Bowen, J.Bacteriol, 1981). Mapping revealed that the photosynthesis gene cluster was on the main chromosome. Remarkably chromosome transfer occurred from a site right next to the photosynthesis gene cluster with early transfer of the entire cluster into the recipent cell. This provides a potential mechanism for the evolution and spread of photosynthesis genes. A clone bank of RS601 was constructed using pHC79:: Tn5deltaBamH1. This vector allowed cosmid cloning into the BamH1 site of Tn5. These Tn5 cosmid clones were transposed onto the broad host range plasmid pR751. The ability to transfer the entire cosmid clone bank to a wide range of bacteria led to the first cloning and heterologous expression of a carotenoid gene cluster (Pemberton&Harding,Current Microbiology,1986 & 1987).This indicated that genes involved in photosynthesis could be transferred to and expressed in a range of unrelated non-photosynthetic bacteria. Subsequent heterologous expression of carotenoid genes in an increasing variety of plants led to the production of foods enriched in the precursors of vitamin A e.g. Golden Rice (Erik Stokstad, Science Nov 20, 2019) . Vitamin A deficiency is the major preventable cause of blindness in children under 5 years of age; it affects up to 500,000 children each year. Using the same clone bank in mapping experiments in Rhodobacter sphaeroides I observed a few pale colonies in which carotenoid biosynthesis was suppressed. Subsequent detailed analysis of one of these cosmids led to the discovery of the long sought master regulator (PpsR) of bacterial photosynthesis and provided the first detailed insight into the mechanism by which bacterial photosynthesis is regulated at the molecular level (A Gene from the Photosynthetic Gene Cluster of Rhodobacter sphaeroides Induces trans Suppression of Bacteriochlorophyll and Carotenoid Levels in R.sphaeroides and R.capsulatus (R.J.Penfold and JM Pemberton, Current Microbiology, 1991; Sequencing, Chromosomal Inactivation and Functional Expression in E.coli of ppsR a Gene which represses carotenoid and bacteriochlorophyll synthesis in Rhodobacter sphaeroides. RJ Penfold and JM Pemberton. J.Bacteriol May 1994).Early studies by Cohen-Bazire, Sistrom and Stanier (1957) revealed that oxygen and blue light had varying effects on photosynthesis in Rhodobacter. The effect of oxygen was profound. The effect of blue light was more muted. The initial sequencing of ppsR (Penfold and Pemberton, 1994) revealed the presence of only two cys residues suggesting a possible mechanism for the profound effect of oxygen on PpsR repressor activity. Studies of conformational changes/repressor activity of PpsR in the presence and absence of oxygen have produced mixed results(Gomelsky et al.,2000;Masuda and Bauer.,2002). In contrast the muted effect of blue light on photosynthesis appears to be due to the blue light sensitive, anti-repressor AppA. (Gomelsky and Kaplan,1995). It is not known if any other environmental signals modulate PpsR activity.The rhodobacter research led to the construction of pJP5603 which allowed the precise insertion of a defined segment of DNA into a bacterial genome (Penfold and Pemberton,1992 ; Zordan,Beliveau,Trow,Craig and Cormack, 2015). The technique was used to either add functional genes or groups of genes to a precise location in the genome or to precisely target and inactivate individual genes. The site of insertion/mutagenesis is tagged with an antibiotic resistance gene. This process is known as “recombineering” ( Zhang et al., 1988). As with all forms of mutagenesis there are “off target” mutations. The consequences of such ”off target” mutations can range from minimal to extensive.
In a study of a range of genes encoding secreted enzymes involved in the degradation of naturally-occurring biological polymers e.g xylanases, cellulases,amylases, chitinases etc I attempted to obtain secretion genes from Chromobacterium violaceum. Again using the pHC79:: Tn5deltaBamH1 vector used in the study of the photosynthesis genes (Pemberton&Harding,Current Microbiology,1986 & 1987) I constructed a cosmid clone bank of C.violaceum. The clone bank I constructed did not produce secretion genes but instead 2-3 of the clones expressed the intense purple pigmented violacein in E.coli(Pemberton,1986). Subsequent subcloning revealed the gene cluster occupied 8kb and transposon mutagenesis revealed intense blue and intense green intermediates. (Pemberton et.al.,Current Microbiology,1991). I am grateful to Trudy Grossman for the detailed study of this cluster which included sequence analysis and functional characterisation of the violacein biosynthetic pathway (August et al., 2000). The functional analysis of the violacein gene cluster revealed that VioA VioC and VioD belong to the PheA(phenol) /TfdB (2,4-D) group of FAD dependant mono-oxygenases. TfdB is encoded by the 2,4-D degradation gene cluster of the broad host range IncP plasmid pJP4 carried by Ralstonia eutropha JMP134. This provides a link between the degradation of a man-made molecule-2,4-D and the synthesis of an anti-tumour antibiotic-violacein. Remarkably, under certain circumstances this 2,4-D degradation pathway can convert 2,4-D into the well known plant antibiotic-protoanemonin (Blasco,R et al., 1995).In 1983 Burt Ensley , Barry Ratzkin and co-workers (Ensley et al.,Science,1983) discovered that the naphthalene dioxygenase gene from Pseudomonas putida enabled E.coli K12 to synthesise the famous blue dye indigo from tryptophan; a second gene, VioD, from the violacein gene cluster also enabled E.coli K12 to produce indigo (Cheah et al.,Acta Crystallographica,1998). Further studies using the violacein gene cluster led to the development of techniques and vectors that should allow cloning and stable, high level expression of more antibiotic biosynthesis pathways in E.coli K12, particularly pathways from the prolific antibiotic producers the Streptomycetes providing novel antibiotics in the fight against antibiotic resistant pathogens (Sarovich and Pemberton,2007; Philip,Sarovich and Pemberton,2008 & 2009;Ahmetagic & Pemberton, 2010 & 2011;Ahmetagic, Philip ,Sarovich,Kluver and Pemberton,2011).An article published in June 2013 by Stevens and co-workers PLoS ONE 8(5) showed that a native gene cluster from Streptomyces rimosus encoding tetracycline can be directly expressed in E.coli K12.
For the first time researchers have showed the expression of the violacein gene cluster in a eukaryote-the yeast Saccharomyces cerevisiae (Lee et al., 2013). Such a discovery may indicate that the violacein gene cluster can be expressed in organisms which range from microbes to man. It may also indicate that major pathways from microorganisms can be engineered and expressed in a range of eukaryotes. Since violacein is a potent anticancer agent it is of interest to determine if the violacein cluster engineered into bacteria of the microbiome of an animal reduces cancer rates. Alternatively it may be possible to engineer the violacein pathway directly into an animal and observe if cancer rates are reduced. In view of the purported prokaryotic ancestry of eukaryoyic organelles such as mitochondria and chloroplasts ,one possible way of boosting violacein synthesis in eukaryotic cells could be to integrate the violacein gene cluster into organelle DNA.
Finally, violacein is chemically related to the well known anti-cancer drug staurosporine and possesses anticancer, antifungal, anti-parasite, antibacterial and antiviral activities;it might be possible to synthesise structural variants of violacein with more potent activity against various cancers and drug/antibiotic resistant pathogens. Interestingly is now known that violacein producing bacteria associated with the skin microbiome of certain frogs provides some protection against extinction by the worldwide spread of ‘chytrid’ fungus(Harris et.al., 2009). In addition, frogs have been used in cancer studies and may provide a simple model to test the anticancer properties of violacein. Since the violacein gene cluster is expressed in a wide range of bacteria ( Dr D S Philip, personal communication;D.S/Philip.PhD Thesis 2010) and has potent activity against the malarial parasite Plasmodium falciparum and other mosquito borne parasites, there is the possibility that mosquitoes engineered to carry the violacein gene cluster might be resistant to parasite infection. The cluster could be stably incorporated in the genomes of bacteria normally inhabiting the surface or the gut of the mosquito.A recent patent application (United States Patent Application 20170280730) indicates that Chromobacterium introduced into the microbiome of mosquitoes is useful for the prevention of transmission of malaria and dengue virus.In addition, chemical modification of violacein may produce drugs with even higher levels of activity against parasites including the malarial parasite ( Wilkinson et al., 2020). Violacein has activity against the pandemic virus Covid19 and there is some knowledge of its mode of action (Duran et al., 2021). Testing may reveal if it has activity against both Kappa and Delta Covid19 variants.Violacein can inhibit infection by HIV and COVID (Doganci et al., 2022)
Fellow, American Society for Microbiology
Fellow, Australian Society for Microbiology
Selected Publications:
Ahmetagic, Adnan, Philip, Daniel S., Sarovich, Derek S., Kluver, Daniel W. and Pemberton, John M. (2011) Plasmid encoded antibiotics inhibit protozoan predation of Escherichia coli K12. Plasmid, 66 3: 152-158. doi:10.1016/j.plasmid.2011.07.006
Ahmetagic, Adnan and Pemberton, John M. (2011) Antibiotic resistant mutants of Escherichia coli K12 show increases in heterologous gene expression. Plasmid, 65 1: 51-57. doi:10.1016/j.plasmid.2010.11.004
Ahmetagic, Adnan and Pemberton, John M. (2010) Stable high level expression of the violacein indolocarbazole anti-tumour gene cluster and the Streptomyces lividans amyA gene in E. coli K12. Plasmid, 63 2: 79-85. doi:10.1016/j.plasmid.2009.11.004
Philip, Daniel S., Sarovich, Derek S. and Pemberton, John M. (2009) Complete sequence and analysis of the stability functions of pPSX, a vector that allows stable cloning and expression of Streptomycete genes in Escherichia coli K12. Plasmid, 62 1: 39-43. doi:10.1016/j.plasmid.2009.03.002