Molecular Sciences Research Booklet 2021/2022 - Macquarie University
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DEPARTMENT OF MOLECULAR SCIENCES
Faculty of Science and Engineering
Molecular Sciences
Research Booklet
2021/2022
epartment of Chemistry and Biomolecular Sciences 1
2021/2022 Research in the Department of Molecular Sciences Macquarie University’s Department of Molecular Sciences (MolSci) is integrating chemical and biomolecular sciences to achieve a sustainable environment, understand health and disease, and advance new molecular technologies. The Department has experienced, motivated research‐active staff with a unique research culture comprising a combination of chemistry and biomolecular sciences and this booklet describes those research interests. The booklet introduces the Department and helps identify research interests. Clearly, the outlines here are very brief and general, so please contact staff offering projects that are of interest to you. Members of the Research Committee are always available to assist students, postdocs and visiting researchers in finding a suitable project amongst Molecular Sciences research activities. FIND OUT MORE Macquarie University NSW 2109 Australia T: +61 (2) 9850 8275 mq.edu.au/molsci CRICOS Provider 00002J 2 Department of Molecular Sciences
2021/2022
Research Clusters
Sustainable Chemical Structural & Synthetic
Molecular Omics
Systems Biology
Amy Cain Alf Garcia-Bennett Louise Brown
Paul Haynes Ian Jamie Paul Jaschke
Nicki Packer Joanne Jamie Briardo Llorento
Giuseppe Palmisano Peter Karuso Lindsay Parker
Ian Paulsen Fei Liu Anwar Sunna
Shoba Ranganathan Andrew Piggott Tom Williams
Sasha Tetu Alison Rodger Robert Willows
Morten Thaysen-Andersen Koushik Venkatesan
Yuling Wang
Note that many staff have interests across more than one Research Cluster
Department of Molecular Sciences 3
2021/2022 Table of contents MolSci Research Clusters ..................................................................................................................... 3 Associate Professor Louise Brown – Protein Biophysics ..................................................................... 6 Dr Amy K. Cain – Pathogen Genomics for Antibiotic Discovery and New Resistance Genes ............ 8 Dr Alfonso Garcia-Bennett – Materials Science and Nanomedicine ................................................ 10 Professor Paul A. Haynes – Plant, Environmental and Bioarchaeological Proteomics .................... 12 Dr Ian Jamie – Chemical Ecology, Atmospheric Chemistry and Chemical Education ..................... 14 Associate Professor Joanne Jamie – Bio-Organic and Medicinal Chemistry and Science Outreach 16 Dr Paul Jaschke – Synthetic Biology .................................................................................................18 Professor Peter Karuso – Chemical Biology and Drug Discovery...................................................... 20 Dr Fei Liu – Biomimetic Catalysis and Systems Chemical Proteomics .............................................22 Dr Briardo Llorente – Synthetic Biology and Evolution ...................................................................24 Distinguished Professor Nicki Packer – Glycomics and Glycoproteomics ........................................ 26 Dr Lindsay Parker – Nano-Neuroscience ......................................................................................... 28 Distinguished Professor Ian Paulsen – Microbial Genomics.............................................................30 Associate Professor Andrew Piggott – Natural Products Biodiscovery .............................................32 Professor Shoba Ranganathan – Bioinformatics and Computational Biosciences ........................... 34 Professor Alison Rodger – Biomacromolecules Structure and Function .......................................... 36 Professor Anwar Sunna – Synthetic Biology and Nanobiotechnology .............................................. 38 Dr Sasha Tetu – Environmental and Applied Microbiology .............................................................. 40 Dr Morten Thaysen-Andersen – Analytical Glycobiology and Glycoimmunology .......................... 42 Associate Professor Koushik Venkatesan – Materials Chemistry, Optoelectronic Devices and Sensors ............................................................................................................................................... 44 Associate Professor Yuling Wang – Nanobiotechnology for in-vitro Diagnosis ............................... 46 Dr Tom Williams – Synthetic Biology............................................................................................... 48 Professor Robert Willows – Biomolecular Chemistry .......................................................................50 4 Department of Molecular Sciences
R
Department of Molecular Sciences 5
2021/2022
STRUCTURAL BIOLOGY
Associate Professor Louise Brown
louise.brown@mq.edu.au
Room: 6WW 305 T: (02) 9850 8294
https://researchers.mq.edu.au/en/persons/louise-brown
BIOPHYSICS GROUP - STRUCTURAL BIOLOGY
Many key physiological processes are controlled at a Figure 1: “Spin Labeling” - the
molecular level by large multi-protein complexes. attachment of a spin label to the
side chain of a cysteine residue that
These complexes are often prone to disease-
has been introduced into a specific
producing mutations. Research in the lab focuses on site on the protein by site-directed
‘pushing the limits’ of structural techniques to reveal mutagenesis.
structure and movement in several large dynamic
protein complexes, including the Troponin complex –
the ‘ON’ switch for muscle contraction [ref 1].
Due to the large size and the dynamic nature of the muscle
Troponin complex, its structure is difficult to determine using
conventional biophysical methods.
The focus in our group is to therefore use ‘reporter-probe’ based
spectroscopic methods to study these challenging protein
systems. We use Site-Directed Spin Labeling methods to
attach small fluorescent or magnetic chemical labels to targeted
regions of interest on the protein complex (Fig. 1). This approach
enables the structure and dynamics of the proteins to be revealed
using spectroscopic techniques including Nuclear Magnetic
Resonance (NMR) (Fig. 2), Electron Paramagnetic Resonance
(EPR) and Fluorescence Spectroscopy [for examples, see refs 2,
3, 4]. These biophysical approaches which unravel the complex
intricacies of protein-protein interactions have outcomes
pertinent to medical science. We can now better understand why
Figure 2: “Spin Labeling”, paired with NMR, is genetic mutations lead to heart diseases such as hypertrophic
used to obtain high-resolution structural detail of cardiomyopathy.
proteins and reveal protein conformationalchanges
and dynamics accompanying function.
MATERIAL SCIENCE – PURPOSE DESIGNED NANOPARTICLES
Bottom-up synthesis approaches provide better control for
synthesizing nanomaterials with desired properties for various
functions. For example, nanodiamonds (< 100nm) have
emerged from primarily having an industrial and mechanical
applications base, to potentially underpinning sophisticated
new technologies in quantum science and biology. Due to the
unique chemical and physical stability of diamond, and our
ability to modify their surface chemistry and also control their
colour centre, nanodiamonds are an attractive nanoparticle
tool that can be used for bio-imaging and bio-tracking – even Figure 3: Nanodiamonds conjugated to a biological
down to a single-molecule level! filament. Single molecule imaging of nanodiamonds.
We are exploring applications ranging from using nanodiamonds as superior biological markers to, potentially,
developing novel bottom-up approaches for the fabrication of hybrid quantum devices that would bridge across
the bio/solid-state interface [for examples, see refs 5-11].
6 Department of Molecular Sciences
2021/2022
STRUCTURAL BIOLOGY
SYNTHETIC BIOLOGY - PRODUCTION OF BIOHYDROGEN
With Professor Robert Willows, we use Synthetic Biology
techniques to engineer bacteria to efficiently produce
hydrogen from renewable biomass such as sugar and starch.
The goal is to engineer a bacterial system so that it has a long
half life of hydrogen production, is stable in the presence of
molecular oxygen, and has an efficiency similar to that
achieved for bio-ethanol production. We are using synthetic
DNA constructs combined with strain engineering and rapid
screening techniques for measurement of hydrogen
production.
This research has strong links with industry and is funded by
Figure 4: Engineering of bacteria for bio-hydrogen an ARENA renewable energy grant.
production.
Projects in our lab would suit students keen to work at the interface of biology, chemistry
and physics with backgrounds in any of the following: molecular biology, biochemistry,
protein chemistry, physical chemistry (spectroscopy), organic chemistry, nanotechnology,
synthetic biology or computational chemistry. Our group has a strong focus of engaging
with industry in both the energy (hydrogen) and quantum science sectors.
Selected Publications
1. Kachooei, E., Cordina, N. M. & Brown, L. J. (2019) Constructing a Molecular Movie of Troponin using Site
Directed Spin Labeling: EPR & PRE-NMR. Biophysical Reviews, 11:621-39.
2. Kachooei, E., Cordina, N. M., Potluri, P. R., Guse J. A., McCamey D. & Brown, L. J. (2021) Phosphorylation of
Troponin I finely controls the positioning of Troponin for the optimal regulation of cardiac muscle contraction. J
Molecular & Cellular Cardiology, 150:44-53.
3. Potluri, P. R., Cordina, N. M., Kachooei, E. & Brown, L. J. (2019). Characterization of the L29Q Hypertrophic
Cardiomyopathy Mutation in Cardiac Troponin C by Paramagnetic Relaxation Enhancement Nuclear Magnetic
Resonance. Biochemistry 58: 908-917
4. Cordina NM, Liew CK, Fajer PG, Mackay JP, Brown LJ (2014) Ca2+-induced PRE-NMR changes in the troponin
complex reveal the possessive nature of the cardiac isoform for its regulatory switch. PloS one 9 (11), e112976
5. T Boele, DEJ Waddington, T Gaebel, E Rej, Ajay Hasija, LJ Brown, DR McCamey, DJ Reilly (2020), Tailored
nanodiamonds for hyperpolarized 13C MRI. Physical Review B 15:155416.
6. J White, C Laplane, RP Roberts, LJ Brown, T Volz, DW Inglis. (2020) Characterization of optofluidic devices for
the sorting of sub-micrometer particles. Applied optics 59 (2), 271-276
7. Garcia-Bennett, A. E., Everest-Dass, A., Moroni, I, Rastogi, I. D., Parker, L. M., Packer, N. H. & Brown, L. J. (2019).
Influence of surface chemistry on the formation of a protein corona on nanodiamonds. Journal Material Chemistry
B, 7:3383-3389
8. Bradac, C., Rastogi, I. D., Cordina, N. M., Garcia-Bennett, A. & Brown, L. J. (2018). Influence of surface
composition on the colloidal stability of ultra-small detonation nanodiamonds in biological media. Diamond and
Related Materials, 83: 38-45
9. Bradac C, Say JM, Rastogi ID, Cordina NM, Volz T, Brown LJ (2016) Nano-assembly of nanodiamonds by
conjugation to actin filaments. Journal of Biophotonics 9: 296-304
10. Geiselmann M, Juan ML, Renger J, Say JM, Brown LJ, et al. (2013) Three-dimensional optical manipulation of a
single electron spin. Nature Nanotechnology, 8: 175–179
11. Say JM, Vreden C, Reilly D, Brown LJ, et al. (2011) Luminescent Nanodiamonds for Biomedical Applications
Biophysical Reviews. Biophysical Reviews, 3:171-184
Department of Molecular Sciences 7
2021/2022
PATHOGEN GENOMICS
Dr Amy K. Cain
amy.cain@mq.edu.au
Room: 6WW208 T: (02) 9850 8206
https://researchers.mq.edu.au/en/persons/amy-cain
PATHOGEN GENOMICS FOR ANTIBIOTIC DISCOVERY & NEW RESISTANCE GENES
More than ever we need a new arsenal to fight the microscopic war against bacteria – especially as antibiotic
resistance rates continue to sky-rocket. The World Health Organisation has recognised antibiotic resistance as
one of the “greatest threats to global health, food security, and development today”. Thus, it is critical to study
antibiotic resistance in great molecular detail and monitor new resistance genes, as well as to look for new
antibiotic targets to develop therapeutically. Our research group is firmly rooted in using cutting edge genomics
techniques to understand antibiotic resistance mechanisms, discover new antibiotic targets and uncover
detailed mechanisms of action (MOA) for novel antimicrobials and current empirical antibiotic therapies.
CUTTING EDGE GENOMICS TECHNIQUES TO STUDY ANTIBIOTIC RESISTANCE
We have pioneered the Transposon directed insertion-site sequencing (TraDIS) method, which combines large-
scale random mutagenesis and whole genome sequencing, to assay the fitness of every gene in the bacterial
genome simultaneously, under any
selection (1,2). We have applied this
method to tens of G-ve and G+ve bacterial
species including hospital ESKAPE
pathogens, environmental and gut strains
across many assays, especially antibiotic
resistance (3), but also in bacteriophage
selection (4), motility (5), animal infection
models (6), and sporulation (7). We
currently have projects open using TraDIS
(learning both the lab and bioinformatics
side) to explore gene function in bacterial
genomes, and identify new antibiotic resistance genes as well as novel therapeutic targets.
UNDERSTANDING THE GENETICS OF ANTIBIOTIC SYNERGY
Our research using genomic techniques also focuses on gaining a
detailed molecular understanding of antibiotic synergy (8).
Antibiotic combination therapy presents a rare opportunity to
revive failing options within our existing arsenal of antibiotics
and is a potent tool to combat multi-drug resistant bacterial
infections. Shockingly, however, we have little to no
understanding of the basic molecular mechanisms underlying
antibiotic synergy. Preliminary studies performed previously in
our lab using TraDIS show that treatment with 2 synergistic
antibiotics separately and together yielded a unique gene set
during the synergistic reaction. Laboratory follow-ups of these
synergy-specific genes identified the first ever antibiotic
synergistic resistance gene, which only gives resistance to both
antibiotics together, but not to either of the individual antibiotics
separately. This preliminary work, together with a handful of
published studies indicate that unique mechanisms of action occur during synergistic killing compared with
8 Department of Molecular Sciences
2021/2022
PATHOGEN GENOMICS
those of the original antibiotics. Understanding these synergy-specific mechanisms of killing and identifying
any secondary drug targets opens up the possibility of improving combination therapy to minimise adverse
side-effects. Further, these unknown secondary targets represent an untapped reservoir of primary drug targets
that will help the discovery of safe and effective antibiotics in the future. Elucidating these complex interactions
has only become possible recently with the advent of high-throughput methods, like TraDIS. We have a current
ARC grant on this area of research and many projects within this space.
TESTING IN VIVO TOXICITY AND EFFICACY OF NEW ANTIBIOTICS IN GALLERIA
Galleria caterpillar larvae are an effective, low-cost and ethical model organism, used routinely in Europe and
America for numerous applications including infection models, pharmacological and chemical toxicity
studies, microbe-microbe or microbe-host
interactions and bioremediation (read
more with our review (9)). The Galleria
Research Facility is uniquely positioned as
it houses dynamic climate control
chambers (37’C and others) for larvae
breeding and experiments, plus
equipment for high-throughput pathogen
manipulation in a safe PC2 setting.
We have projects testing the toxicity,
efficiency and dosage as well as
mechanism of action of a number of new
antibiotics that will one day be used to
save the world. This is the first time these
potentially life-saving drugs will be put in
animals, and using Galleria are an ethical
alternative to mice.
Selected Publications
1. AK Cain, L Barquist, AL Goodman, IT Paulsen, J Parkhill, T van Opijnen A decade of advances in transposon-
insertion sequencing Nature Reviews Genetics 21 (9), 526-540 2020 (Review)
2. L Barquist, M Mayho, C Cummins, AK Cain, CJ Boinett, AJ Page, GC Langridge, JA Keane, J Parkhill, TraDIS
sequencing & analysis for dense transposon libraries, Bioinformatics, 2016
3. AK Cain* B Jana* CJ Boinett, MC Fookes, J Parkhill, L Guardabassi, Identification of antimicrobial helper drug
targets in multidrug-resistant Klebsiella pneumoniae ST258 by genome-wide gene-drug interaction profiling,
Scientific Reports 7 2017
4. L Cowley, A Low, D Pickard, … D Gally, J Parkhill, C Jenkins, and AK Cain. Transposon insertion sequencing
elucidates novel gene involvement in phages T4 and T7 susceptibility and resistance in Escherichia coli O157, Mbio,
2018
5. LM Nolan, CB Whitchurch, L Barquist, .. IG Charles, A Filloux, J Parkhill and AK. Cain, A global genomic approach
uncovers novel components for twitching motility-mediated biofilm expansion in Pseudomonas aeruginosa, Mbio,
2018
6. A Charbonneau, OP Forman, AK Cain, G Newland, C Robinson, J Parkhill, J Leigh, D Maskell, A Waller, Defining the
ABC of gene essentiality in streptococci BMC Genomics 2017
7. Dembek M, Barquist L, Boinett CJ, Cain AK et al., High-throughput analysis of gene essentiality and sporulation in
Clostridium difficile, Mbio, 2015
8. GJ Sullivan, NN Delgado, R Maharjan, and AK Cain How antibiotics work together: Molecular mechanisms behind
combination therapy, Current Opinion in Microbiology 57, 31-40 2020
9. H Dinh, L Semenec, SS Kumar, FL Short, and AK Cain, Microbiology's next top model: Galleria in the molecular age
Pathogens and Disease 2021
Department of Molecular Sciences 9
2021/2022
NANOSTRUCTURED BIOMATERIALS
Dr Alfonso Garcia-Bennett
alf.garcia@mq.edu.au .
Room: 4WW337 T: (02) 9850 8285
https://researchers.mq.edu.au/en/persons/alf-garcia-bennett
NANOSTRUCTURED BIOMATERIALS
We are interested in understanding and controlling self-assembly processes to prepare new materials with structural
order at the nanoscale. We focus on silica based nanostructured particles which are being developed for applications
in nanomedicine and pharmaceutical drug delivery. Our aim is to better understand the interphase between biology
and inorganic materials.
We make materials that are compatible with the human body, interacting with biological substrates at the
nanoscale (e.g. membrane proteins). They include materials that are helpful to delivery drugs more efficiently,
to understand their mode of actions and to enable the discovery of new therapeutic agents.
SYNTHESIS OF HYBRID NANOSTRUCTURED MATERIALS
Our approach is to focus on the organization of discrete number of chemical units into higher ordered
structures and the fundamental forces that bind these units together. We use bio-inspired organic templates,
such as nucleotides (e.g. guanosine monophosphate) or vitamins (e.g. folic
acid) that can be co-assembled in the presence of silica precursors
resulting in hybrid (organic and inorganic) nanostructured materials.
These show structural order at both atomic and meso scales. Properties of
the organic template (e.g. chirality) can be transcribed on to the silica wall,
whilst this gives structural support back to the organic template. We
perform structural characterization by electron microscopy and X- ray
diffraction.
We aim to determine how the properties of the supramolecular templates
(e.g. optical properties) are affected by its ordering within the inorganic
silica and how we can use these materials for chiral separation.
DRUG DELIVERY PROPERTIES OF NANOPOROUS MATERIALS
We are interested in the properties of mesoporous silica materials which have ordered pores between 2-50 nm
and amorphous silicon dioxide walls. The large surfaces areas, which may be as high as 1500 m 2/g, are
composed of silanol groups (Si-OH) which may be further functionalized for further bioconjugation or
encapsulation of more complex groups such as for fluorophores or pharmaceutical drugs.
Over the last decade, the field of ordered mesoporous materials has seen an expansion on the number of
reported biomedical applications using both nano- and micron- sized particles. Mesoporous materials
selectively interact with biological systems by means of their surface and morphological properties opening
new doors for therapy development in drug delivery, including drug targeting strategies. Within drug
formulation, the enhancement of apparent solubility of pharmaceutical compounds in order to improve their
10 Department of Molecular Sciences2021/2022
NANOSTRUCTURED BIOMATERIALS
bioavailability and pharmacokinetic properties is emerging as an area where tangible industrial and clinical
benefit ca be provided.
Our results show that confinement of pharmaceutical drugs within mesoporous silica structures prevents the
crystallization of the compound within the pore space which improves the drug solubility of the compound and
its eventual bioavailability. Mesoporous silica particles exhibit a diffusion-controlled mechanism of drug
release and can lead to an enhancement of solubility than a similar dose of the unloaded, free drug. These
values can be reproduced in vivo and can be the basis for new therapeutic uses of established drugs.
Our research now centers in the relation between chemical properties of the drug compound such as molecular
weight, solubility, and crystallization behavior; and the range of confinement (inhibition of crystallization,
stabilization of the amorphous state, or changes to molecular mobility) that can be achieved in a variety of
mesoporous pore structures.
THE PROTEIN CORONA: A PARTICLE BIOLOGICAL IDENTITY CARD
The biological behavior of nanoparticles within the body is determined by adsorbed protein layers rapidly
forming in contact with human plasma or cellular media. Understanding how these layers are formed, and how
the body interprets these fundamental signals is critical for the realization of nanomedicine based therapies
during the next decades. This project envisages the protein corona as a tool to direct the behavior of
nanoparticles, utilizing imaging techniques to address the lack of mechanistic information on the relation
between the nanoparticle surface and its biological interactions.
Selected Publications
1. Moroni, I., et al. (2021). Pharmacokinetics of exogenous melatonin in relation to formulation, and effects on sleep: a
systematic review. Sleep Medicine Reviews, 101431
2. Giri, K., Lau, M., Kuschnerus, I., Moroni, I., Garcia-Bennett, A. E. (2020). Effect of a protein corona on the
fibrinogen induced cellular oxidative stress of gold nanoparticles. Nanoscale 12 (10), 5898-5905.
3. Huang, Y., Vidal, X., Garcia-Bennett, A. E. (2019). Chiral Resolution using Supramolecular‐Templated
Mesostructured Materials. Angew.Chem. Int. Ed., 58(32), 10859-10862.
4. Lau, M., Giri, K., Garcia-Bennett, A. E. (2019). Antioxidant properties of probucol released from mesoporous
silica. Europ. J. of Pharm. Sci. 138, 105038, 2(32), 5265-5271.
5. Garcia-Bennett, A. E. (2011). Synthesis, toxicology, and potential of ordered mesoporous materials in
nanomedicine. Nanomedicine, 6(5), 867-877.
6. Xia, X., Zhou, C., Ballell, L., Garcia-Bennett, A. E. (2012). In vivo Enhancement in Bioavailability of Atazanavir in
the Presence of Proton-Pump Inhibitors using Mesoporous Materials. Chemmedchem, 7(1), 43-48.
Department of Molecular Sciences 112021/2022
PLANT AND BIOARCHAEOLOGICAL PROTEOMICS
Professor Paul A. Haynes
paul.haynes@mq.edu.au
Room: 6WW309 T: (02) 9850 6258
https://researchers.mq.edu.au/en/persons/paul-haynes
PLANT AND BIOARCHAEOLOGICAL PROTEOMICS
Research in our laboratory focusses on applying quantitative proteomics approaches in plant biology and
bioarchaeology. Weuse mass spectrometry to identify and quantify proteins present inside cells, and we are
constantly refining the analytical approaches we use, in terms of both protein chemistry and bioinformatics.
We aim to understand what happens at the molecular level when a plant is exposed to changes in its external
environment. We have published a number of studies on the effects of temperature stress on rice cells and
seedlings, drought stress on rice plants, temperature stress on grape cells, and drought stress and changes in
day length on grape vines. We also work the identification of proteins from ancient artefacts, with the aim of
uncovering new information which can be highly valuable in the historical context.
ANALYSIS OF STRESS RESPONSE IN PLANTS
Drought stress affects plants severely and is a real
problem facing our society in the face of future
climate change.
The figure to the right (above) shows rice plants
from a previous study in our laboratory involving
analysis of drought signalling. We were able to show
using split-rooted pots that the molecular signal for
drought stress is communicated from droughted
roots to well-watered roots, but not the other way
around.
The figure to the right (below) is a heat map
generated from label-free quantitative shotgun
proteomic analysis of rice cells exposed to five
different temperatures. The cluster on the right
corresponds to cells subjected to 3 days at 44 C, and
is clearly the most different to the others. This is a
summary of the identification and quantification of
more than 2500 proteins, generated from more
than two million spectra of raw mass spectrometric
data. We also developed our own software to enable
quantification of those proteins which are
differentially expressed between different
environmental conditions.
We are currently analysing protein expression
profiles in a range of different rice varieties and
species, and how these change in response to stress.
We are working on an ARC funded Discovery
Project involving reengineering of rice root
architecture, to enable plants to grow steeper and
deeper roots and hence become more efficient at
water usage. This work is being performed in
collaboration with Prof. Brian Atwell in Biological
Sciences, Dr Mehdi Mirzaei, and Prof. Hosseini
Salekdeh at ABRII in Tehran.
12 Department of Molecular Sciences2021/2022
PLANT AND BIOARCHAEOLOGICAL PROTEOMICS
BIOARCHAEOLOGICAL PROTEOMICS
The second main area of work in our laboratory is in bioarchaeological
proteomics, which involves identification of proteins from ancient
materials recovered from archaeological sites. Some of our recently
published work includes the analysis of ancient skin samples recovered
from 4000-year-old Egyptian mummies, where we were able to
provide evidence of acute inflammation and severe response, and
suggest a possible cause of death. We are continuing to expand on this
work, as we have access to a large number of archaeological samples
from various collaborators in ancient history departments at MQ,
University of Sydney, and elsewhere. This includes: skin, muscle, bone,
resin and textile samples from several different ancient Egyptian
mummies; preserved brain tissue from bodies recovered from a
mediaeval Belgian monastery; and
several teeth recovered from a
Neolithic mesoamerican tomb.
Analysis of ancient materials is
difficult and exacting work, but
represents exciting interdisciplinary research using cutting edge molecular
technologies to reveal biological information which is highly valuable in the
archaeological context. We are also developing novel minimally invasive
sampling techniques, which will enable us access a wider range of sample
materials held in museum collections, since the analysis will not involve
destruction of valuable ancient artefacts.
Selected Publications
1. Hamzelou S, Kamath L, Masoomi-Aladizgeh F, Johnsen M, Atwell BJ and P.A. Haynes. Wild and Cultivated
species of rice have distinctive proteomic responses to drought. Int. J. Mol. Sci. 2020, 21(17) 5980
2. Hamzelou S, Pascovici D, Kamath K, Amirkhani A, McKay M, Mirzaei M, Atwell BJ and P.A. Haynes.
Proteomic responses to drought vary widely among eight diverse genotypes of rice (Oryza sativa). Int. J.
Mol. Sci. 2020, 21(1) 363
3. Wu Y, Mirzaei M, Pascovici D, Haynes PA, Atwell BJ. Proteomes of Leaf-Growing Zones in Rice Genotypes
with Contrasting Drought Tolerance. Proteomics. 2019 May;19(9)
4. Rahiminejad M, Ledari MT, Mirzaei M, Ghorbanzadeh Z, Kavousi K, Ghaffari MR, Haynes PA, Komatsu S,
Salekdeh GH. The Quest for Missing Proteins in Rice. Mol Plant. 2019 Jan 7;12(1):4-6.
5. Wu Y, Mirzaei M, Atwell BJ, Haynes PA. Label-free and isobaric tandem mass tag (TMT) multiplexed
quantitative proteomic data of two contrasting rice cultivar exposed to drought stress and recovery. Data
Brief. 2018 Dec 15;22:697-702
6. Handler DC, Pascovici D, Mirzaei M, Gupta V, Salekdeh GH, Haynes PA. The Art of Validating Quantitative
Proteomics Data. Proteomics. 2018 Dec;18(23):e1800222.
7. George IS, Fennell AY, Haynes PA. Shotgun proteomic analysis of photoperiod regulated dormancy
induction in grapevine. J Proteomics. 2018, May 29
8. Jones J, Mirzaei M, Ravishankar P, Xavier D, Lim do S, Shin DH, Bianucci R, Haynes PA. Identification of
proteins from 4200-year-old skin and muscle tissue biopsies from ancient Egyptian mummies of the first
intermediate period shows evidence of acute inflammation and severe immune response. Philos Trans A
Math Phys Eng Sci. 2016 Oct 28;374(2079).
9. Rattanakan S, George I, Haynes PA, Cramer GR. Relative quantification of phosphoproteomic changes in
grapevine (Vitis vinifera L.) leaves in response to abscisic acid. Hortic Res. 2016 Jun 22;3:16029.
10. Wu Y, Mirzaei M, Pascovici D, Chick JM, Atwell BJ, Haynes PA. Quantitative proteomic analysis of two
different rice varieties reveals that drought tolerance is correlated with reduced abundance of photosynthetic
machinery and increased abundance of ClpD1 protease. J Proteomics. 2016 143:73-82.
Department of Molecular Sciences 132021/2022
CHEMICAL ECOLOGY/ATMOSPHERIC CHEMISTRY/CHEMICAL EDUCATION
Dr Ian Jamie
ian.jamie@mq.edu.au
Room: 4WW236 T: (02) 9850 8293
https://researchers.mq.edu.au/en/persons/ian-jamie
CHEMICAL ECOLOGY AND ATMOSPHERIC CHEMISTRY
Chemicals that are found in trace quantities in the atmosphere can play significant roles in processes that
directly and indirectly affect the quality of our life. Chemicals are used by plants and animals in growth,
development, reproduction and defence. We are interested in understanding the sources, reactions and effects
that these species have.
Understanding the way in which students learn and teachers teach will allow us to develop better teaching and
learning methods.
The research programs described here are examples of what might be investigated. Other projects can be
accommodated if they fall within the general theme of the group’s activities.
ATTRACTANT AND PHEROMONE COMPOUNDS OF ECONOMICALLY IMPORTANT INSECTS AND
THEIR ENVIRONMENT (with Joanne Jamie, MolSci and Phil Taylor, Biology)
Bactrocera fruit flies – a genus of more than 500 species – include some of the
world’s most devastating insect pests of horticulture. Air-borne pheromones are
used by these insects to communicate, and in synthetic form also have potential as
tools for control. Attractant compounds are used to monitor and control fruit fly
populations.
O
We are also interested in how fruit flies react to odours
N produced by bacteria, as some bacteria are pathogens, some
H
are symbionts, and some are key elements of nutrition. How do Bactrocera fruit flies avoid
harmful bacteria and locate beneficial bacteria? Natural enemies of fruit flies, such as predators
and parasites, have a significant impact on the lives of fruit flies but little is known about how O
these flies might counter such threats. One mechanism is through detection and adaptive
response to chemical cues (‘kairomones’) either emitted directly from enemies or deposited as
enemies move through the environment.
O
Projects in these areas may focus on one or more category of compounds, and
may encompass synthesis of novel and known compounds, qualitative and
quantitative analysis of pheromones or
odour emissions (e.g., by GC-MS), and O O
studies of behavioural responses of
Bactrocera fruit flies to these compounds. Activities may include travel for the
collection of emissions and assays to test for biological activity (e.g., GC-
coupled electroantennogram, wind tunnel, fieldtrials).
This work is being done as part of the Centre for Fruit Fly Biosecurity
Innovation (https://www.fruitflyittc.edu.au/), an Australian Research
Council funded Industrial Transformation Training Centre, which is dedicated to providing the Australian
horticulture industries new, sustainable and environmentally friendly tools for controlling fruit fly pests. Our
research aims to protect horticulture industries and market access, and help ensure Australia's food security. We
14 Department of Molecular Sciences2021/2022
CHEMICAL ECOLOGY/ATMOSPHERIC CHEMISTRY/CHEMICAL EDUCATION
work in collaboration with the NSW Department of Primary Industries, the Queensland Department of Agriculture
and Fisheries, Plant and Food Research New Zealand, CSIRO and a number of other organisations.
EMISSIONS OF ORGANIC COMPOUNDS FROM PLANTS
Vegetation emits significant quantities of Volatile Organic Compounds. These emissions
may be correlated with internal chemistry of the plants, and give clues on such things
as the presence of useful compounds, stage of plant development and the maturation
state of fruit. The relatively new technique of Solid-Phase Microextraction (SPME) offers
a route to convenient in situ sampling. SPME combines in one-step sampling and
preconcentration, prior to GC or GC-MS analysis. Our research activity aims at
developing methods of in situ SPME-GC analysis, and to develop a database of VOC
emissions from Australian native vegetation. We are also interested in the ways that
plants and animals use VOCs for signalling and deception purposes.
INDOOR AND OUTDOOR AIR QUALITY: GREENHOUSE GASES, VOLATILE ORGANIC COMPOUNDS
AND SECONDARY ORGANIC AEROSOLS (with CSIRO Energy, North Ryde)
Identifying and quantifying the sources of volatile organic compounds (VOCs) is
important as these compounds are involved in complex chemical and physical
transformations that result in effects such as smog and aerosol formation, and
changes in the oxidative capacity of the atmosphere. Large volumes of VOCs are
emitted from plants (biogenic VOCs) and from human activities (anthropogenic
VOCs). We have a range of projects concerned with identifying and quantifying
VOCs and their sources and looking at the chemical composition of aerosols
formed from these compounds. Of interest at the moment is the fate of carbon
sequestering amines fugitively emitted to the atmosphere.
Selected Publications
1. D.N.S. Cameron, C. McRae, S.J. Park, P. Taylor, & I.M. Jamie, "Vapor pressures and thermodynamic properties of
phenylpropanoid and phenylbutanoid attractants of male Bactrocera, Dacus, and Zeugodacus fruit flies at ambient temperatures”
Journal of Agricultural and Food Chemistry. 68, (2020) 36, p. 9654-9663 10 p.
2. S.J. White, D.E. Angove, L. Kangwei, I. Campbell, A. Element, B. Halliburton, S. Lavrencic, D.N.S. Cameron, I.M. Jamie, M. Azzi,
“Development of a new smog chamber for studying the impact of different UV lamps on SAPRC chemical mechanism predictions
and aerosol formation”, https://doi.org/10.1071/EN18005, published online 13-June-2018
3. G Whiteford et al., “The River of Learning: building relationships in a university, school and community Indigenous widening
participation collaboration”, Higher Education Research & Development, 36 (2017), 1490-1502
4. M.S. Siderhurst, S. J. Park, I. M. Jamie, S. De Faveri, “Electroantennogram Responses of Six Bactrocera and Zeugodacus spp.
to Raspberry Ketone Analogs”, Environmental Chemistry, 14 (2017), 378-384
5. S.J. Park, M.S. Siderhurst, I.M. Jamie, P.W. Taylor, “Hydrolysis of Queensland fruit fly, Bactrocera tryoni (Froggatt), attractants:
kinetics and implications for biological activity”, Australian Journal of Chemistry, 69 (2016), 1162-1166
6. S.J. Park, R. Morelli, B.L. Hanssen, J.F. Jamie, I.M. Jamie, M.S. Siderhurst, P.W. Taylor, “Raspberry Ketone Analogs: Vapour
Pressure Measurements and Attractiveness to Queensland Fruit Fly, Bactrocera tryoni (Froggatt) (Diptera: Tephritidae)”, PLOS
ONE, 11 (2016), e0155827
7. M.S. Siderhurst, S.J. Park, C.N. Buller, I.M. Jamie, N.C. Manoukis, E.B. Jang, P.W. Taylor “Raspberry Ketone Trifluoroacetate,
a New Attractant for the Queensland Fruit Fly, Bactrocera Tryoni (Froggatt)”, Journal of Chemical Ecology, 42 (2016), 156-162
8. K.G.S. Dani, I.M. Jamie, I.C. Prentice and B.J. Atwell, “Species-specific photorespiratory rate, drought tolerance and isoprene
emission rate in plants”, Plant Signaling & Behavior, 10 (2015) e990830
9. K.G.S. Dani, I.M. Jamie, I.C. Prentice and B.J. Atwell, “Increased Ratio of Electron Transport to Net Assimilation Rate Supports
Elevated Isoprenoid Emission Rate in Eucalypts under Drought”, Plant Physiology, 165 (2014) 439-446
10. S.J. White, I.M. Jamie, D.E. Angove, “Chemical characterisation of semi-volatile and aerosol compounds from the photooxidation
of toluene and NOx”, Atmospheric Environment, 83 (2014) 237-244
11. S.J. White, M. Azzia, D.E. Angove and I.M. Jamie, “Modelling the Photooxidation of ULP, E5 and E10 in the CSIRO Smog
Chamber”, Atmospheric Environment, 2010, 44, 5375-5382.
https://www.mq.edu.au/research/research-centres-groups-and-facilities/groups/chemical-
ecology-and-atmospheric-chemistry-group
Department of Molecular Sciences 152021/2022
BIO-ORGANIC AND MEDICINAL CHEMISTRY AND SCIENCE OUTREACH
Associate Professor Joanne Jamie
joanne.jamie@mq.edu.au
Room: 4WW231 T : ( 0 2 ) 9850 8283
https://researchers.mq.edu.au/en/persons/joanne-jamie
BIO-ORGANIC AND MEDICINAL CHEMISTRY AND SCIENCE OUTREACH
Our research is aimed at using bio-organic and medicinal chemistry to develop important healthcare
treatments and to address agricultural problems. Current research is focussed on collaborative partnerships
with Indigenous communities for documentation, biological screening and isolation of bioactive compounds
from ‘bush’ foods and medicines; and studies on isolation and synthesis of fruit fly attractants and analysis of
their effectiveness. Projects on development of educational resources for a science engagement program, the
National Indigenous Science Engagement Program (NISEP), and/or evaluation of the effectiveness of the
program, are also available.
FRUIT FLY ATTRACTANT AND PHEROMONE COMPOUNDS
Bactrocera fruit flies include some of the world’s most devastating insect pests of
horticulture. Air-borne pheromones are used by these insects to communicate, and in
synthetic form also have potential as tools for control. Attractant compounds are used to
monitor and control fruit fly populations. We are interested in the analysis of fruit fly
pheromones to develop new attractants and in understanding the structure activity
relationship (SAR) of attractants to fruit flies to help in the design of better lures. We are
also interested in how fruit flies react to odours produced by bacteria, as some bacteria are pathogens, some
are symbionts, and some are key elements of nutrition. Natural enemies of fruit flies, such as predators and
parasites, have a significant impact on the lives of fruit flies but little is known about how these flies might
counter such threats. One mechanism is through detection and adaptive response to chemical cues
(‘kairomones’) either emitted directly from enemies or deposited as enemies move through the environment.
Projects in these areas may focus on one or more category of compounds, and
may encompass extraction of fruit fly pheromones from fruit fly rectal glands,
synthesis of novel and known compounds as lures, qualitative and quantitative
analysis of pheromones or odour emissions (e.g., by GC-MS), and studies of
behavioural responses of Bactrocera fruit flies to these compounds. Activities
may include travel for the collection of fruit fly volatile pheromone emissions and assays to test for biological
activity (e.g., GC-coupled electroantennogram, wind tunnel, field trials).
ETHNOPHARMACOLOGICAL STUDIES OF CUSTOMARY ‘BUSH’ FOODS AND MEDICINES
Research projects aimed at working with Indigenous people to uncover the
potential of their customary (traditional and contemporary) Indigenous ‘bush’
foods and medicines and to isolate and identify novel bioactive compounds from
them are available.
The rich customary knowledge on plants possessed by Indigenous cultures from
around the world is a proven resource for the provision of commercial native foods,
flavours, fragrances, nutraceuticals, therapeutics, healthcare and agricultural
products. As just one example, approximately 25% of all pharmaceutical products worldwide have originated
from Indigenous medicinal knowledge and the study of this knowledge is of key importance in the discovery of
new drugs. In Australia, for many Aboriginal communities this knowledge is being rapidly lost due to limited
documentation and little chemical or biological investigations of their bush foods and medicines have been
conducted.
16 Department of Molecular Sciences2021/2022
BIO-ORGANIC AND MEDICINAL CHEMISTRY AND SCIENCE OUTREACH
We have established strong partnerships with Aboriginal Elder custodians of customary knowledge and various
projects are available in partnership with them. This includes firsthand documentation of their bush food and
medicines knowledge, conducting antimicrobial and antioxidant assays and undertaking chromatographic
methods and spectroscopic studies to elucidate the compounds responsible for the flora’s medicinal properties.
Projects may also incorporate metabolomics studies of bush foods and medicines and developing
bioinformatics databases to integrate, visualise and analyse both firsthand and public domain customary
medical plant data in order to preserve the customary knowledge of Indigenous people and provide information
that can be used for their cultural and educational purposes and/or development of community healthcare and
neutraceutical products.
NATIONAL INDIGENOUS SCIENCE EDUCATION PROGRAM
Using science as a tool for developing student engagement, the National Indigenous
Science Education Program (NISEP) allows secondary students from low SES regions,
especially Indigenous youth, to succeed in their secondary education and to make the
transition to tertiary education. NISEP is a consortium of Australian universities, high
schools and science and Indigenous outreach organisations. NISEP is an award-
winning program that has tangible positive educational outcomes for participants and
there is demand for its implementation more widely across higher education
institutions. Given this demand, it is essential to have science engagement activities of
the highest calibre and to identify the critical components of NISEP’s success. Projects
will be available to develop effective engagement resources and activities and to build
an evidence base for the effectiveness of NISEP.
Selected Publications
1. Noushini, S., Park, S. J., Jamie, I., Jamie, J. & Taylor, P., Rectal gland exudates and emissions of Bactrocera bryoniae:
chemical identification, electrophysiological and pheromonal functions, In: Chemoecology. 31, 2, p. 137-148 12 p. 2021.
2. Noushini, S., Perez, J., Jean Park, S., Holgate, D., Alvarez, V. M., Jamie, I., Jamie, J. & Taylor, P., Attraction and
electrophysiological response to identified rectal gland volatiles in Bactrocera frauenfeldi (Schiner), In: Molecules.
25, 2020.
3. Vemulpad SR, Harrington D, Jamie JF, Collaborative Partnerships for Recognising and Protecting Traditional
Medicinal Knowledge, In: Stoianoff N, Ed. Indigenous Knowledge Forum – Comparative Systems for Recognising
and Protecting Indigenous Knowledge and Culture, Chapter 8, 207-226: LexisNexis, 2017.
4. Akter K, Barnes EC, Loa-Kum-Cheung WL, Yin P, Kichu M, Brophy JJ, Barrow R, Imchen I, Vemulpad SR, Jamie JF,
Antimicrobial and Antioxidant Activity and Chemical Characterisation of Erythrina stricta Roxb. (Fabaceae), Journal
of Ethnopharmacology, 2016, 185, 171-181.
5. Akter K, Barnes EC, Brophy JJ, Harrington D, Yaegl Community Elders, Vemulpad RS, Jamie JF, Phytochemical
Profile and Antibacterial and Antioxidant Activities of Medicinal Plants Used by Aboriginal People of New South Wales,
Australia, Evidence-Based Complementary and Alternative Medicine, 2016, 2016.
6. Park SJ, Morelli R, Hanssen BL, Jamie JF, Jamie IM, Siderhurst MS, Taylor PW, Raspberry Ketone Analogs: Vapour
Pressure Measurements and Attractiveness to Queensland Fruit Fly, Bactrocera tryoni (Froggatt) (Diptera:
Tephritidae), PLoS One, 2016, 11(5):e0155827.
7. Naz T, Packer J, Yin P, Brophy JJ, Wohlmuth H, Renshaw DE, Smith J, Yaegl Elders Community, Vemulpad SR,
Jamie JF, Bioactivity and Chemical Characterisation of Lophostemon suaveolens – an Endemic Australian
Aboriginal Traditional Medicinal Plant, Natural Product Research, 2016, 30, 693-6.
Department of Molecular Sciences 172021/2022
SYNTHETIC BIOLOGY
Dr Paul Jaschke
paul.jaschke@mq.edu.au
Room: 14EAR357 T: (02) 9850 8295
https://researchers.mq.edu.au/en/persons/paul-jaschke
SYNTHETIC BIOLOGY
Genetically engineered microbes and viruses have the potential to transform
chemical production, therapeutics development, and our entire economy to be more
efficient and sustainable. The Jaschke lab pursues two main research areas to
realise the vision of engineered microbes and viruses to improve human and
environmental health. Our first area of research is focused on engineering initiator
tRNAs to more precisely control when genes turn on and off inside cells. Each
engineered tRNA can be thought of as a chemical ‘wire’ that we can control
orthogonally to all the other wires. We will use these wires or switches to more
precisely control metabolic pathways in cells that produce useful fine or bulk
chemicals or for therapeutic protein or metabolites production.
A second area of our work uses bacteriophage, viruses that infect bacteria, to
develop new antimicrobial therapies. Currently we face a growing problem with
antibiotic resistance in clinics and the community. Natural and engineered
bacteriophage are one way we might tackle this problem. We are currently working
on several different ways to do this through modifying the host-range of model
phages.
DEEP CHARACTERISATION OF A HIGHLY ENGINEERED BACTERIOPHAGE
The phage øX174 has been part of many firsts in science, from being
the first DNA genome sequenced in 1977 (Nature 1977, 265: 687-
695), to the first synthetic genome ‘booted up’ by Craig Venter in 2003
(PNAS 2003, 100: 15440-5), to the first bacteriophage genome
accessioned by MoMA1. The genome of øX174 is interesting from
many perspectives, but one feature that has puzzled and intrigued
scientists over the years is the fact that many of its genes are
overlapped with each other. This creates a genome with highly
compressed information analogous to what happens when music gets
compressed into an MP3 file. Several years ago the genome of øX174
was redesigned to fully decompress (separate) all the overlapped
genes from each other. The resulting virus was shown to be functional but not studied any further 2. The
decompressed øX174 phage will be analysed using microbiological methods to determine viral lifecycle
characteristics, while molecular techniques will be used to determine how RNA and protein expression is
altered from the naturally occurring wild-type øX174 phage.
18 Department of Molecular Sciences2021/2022
SYNTHETIC BIOLOGY
REFINING THE GENOME OF A HIGHLY ENGINEERED BACTERIOPHAGE USING EVOLUTION
This project will aim to improve lifecycle characteristics, such as growth rate, of the fully decompressed
synthetic øX174 genome. Our approach will be to use evolution to refine the genome through iterative rounds
of natural selection followed by sequencing and analysis to understand how the observed genome changes
result in a faster growth phenotype. Evolution is a unique property of biological systems that sets them apart
from the raw material of other engineering fields (Nature 2005, 438: 449-453). Synthetic biology has yet to
fully recognize the utility of evolution in shaping engineered genomes. This project will complement recent
work from our group that has shown that a øX174 genome containing hundreds of silent point mutations can
be improved through an evolutionary process3.
ENGINEERING START CODON FLEXIBILITY WITHIN NATURAL AND SYNTHETIC BACTERIOPHAGE
GENOMES
The vast majority of all known genes, across all known species, use the three DNA letters ATG as their first
(start) codon. Recently in an experimental survey of all 64 possible codons it was found that there may be as
many as 15 codons, that under certain conditions, will function as the start codon for a gene4. This project will
explore the possibility of recoding all the genes of an organism to use non-canonical start codons. This work
will aim to reveal the total functional start codon sequence space available for bioengineering. In this project,
both the wild type øX174 genome as well as the fully decompressed øX174 genome will have the start codon for
each known gene swapped out for a series of non-canonical codons shown to have activity. Genomes will be
constructed and evaluated in high-throughput screens to identify codon combinations that result in viable
phage. Results of this work will contribute to our understanding of how natural genomes are ‘designed’ by
natural selection as well as lead to better understanding of additional ways to tune protein expression from
artificial genetic systems.
Selected Publications
1. Karen D. Weynberg and Paul R Jaschke. (2019). Building Better Bacteriophage with Biofoundries to Combat
Antibiotic Resistant Bacteria. PHAGE: Therapy, Applications, Research. Accepted 30 Sept 2019. DOI:
https://doi.org/10.1089/phage.2019.0005
2. Russel M. Vincent, Bradley W. Wright, Paul R Jaschke. (2019). Measuring amber initiator tRNA orthogonality in a
genomically recoded organism. ACS Synthetic Biology. Accepted 11 March. DOI: 2019. 10.1021/acssynbio.9b00021
3. Hessel A, Quinn J, Jaschke PR. Synthetic øX174 Bacteriophage. Design and Violence Exhibit. Museum of Modern
Art (MoMA). New York, USA
4. Jaschke, P. R., Lieberman, E. K., Rodriguez, J., Sierra, A., and Endy, D. (2012). Virology. A fully decompressed
synthetic bacteriophage øX174 genome assembled and archived in yeast. 434, 278–84.
5. Hecht A, Bawazar L, Glasgow J, Jaschke PR, Cochrane J, Salit M, Endy D (2017). A systematic evaluation of
translation initiation from all 64 codons in E. coli. Nucleic acids research 45 (7), 3615-3626
http://www.jaschke-lab.science/
Department of Molecular Sciences 192021/2022
Professor Peter Karuso
CHEMICAL BIOLOGY AND DRUG DISCOVERY
peter.karuso@mq.edu.au
Room: 4WW232 T: (02) 9850 8290
https://researchers.mq.edu.au/en/persons/peter-karuso
CHEMICAL BIOLOGY @ MQ
Our research interests lie in the application of small molecules to biological systems, which involves new
and exciting multidisciplinary approaches incorporating molecular biology, organic synthesis, analytical
chemistry, NMR spectroscopy, computational chemistry and biochemistry to solving medicinally relevant
problems. We are particularly interested in marine natural products and fluorescent natural products,
their biological activity, biosynthesis and most importantly, their modes of action as drugs and
applications in biotechnology.
CHEMICAL BIOLOGY OF NATURAL PRODUCTS
We focus on changing the way people think about drug discovery by changing the way we work with the
interactions between small molecules and biomolecules. This requires the development of new tools that
accelerate our understanding of how drugs facilitate change in living systems. This paradigm shift in the
relationship between chemical diversity and biological activity will lead to the reinvigoration of the
pharmaceutical industry through the rapid development of new drugs based on natural products.
YEAST SURFACE DISPLAY
The genetic manipulation of yeast to display foreign proteins on their surface as part of a cDNA or genomic
library. Such “libraries” are very useful for the unbiased and rapid identification of proteins that bind to small
molecules. We named this newfield “Reverse Chemical Proteomics” and led to my second spin-out – Hyperdrive
Science Pty Ltd that focused on the application of phage display for the identification of drug binding proteins.
Working in this area requires crossing disciplinary boundaries combining synthetic biology and chemistry so
progress can be slow at times but always exciting and challenging. Current projects include:
• identification of the human, bacterial and Plasmodium targets for bioactive natural products;
• isolation and structure elucidation of new natural products;
• synthesis of biotinylated and fluorescently labelled probes;
• construction of high quality gDNA and cDNA libraries for yeast surface display and methods for
biopanning.
journal cover yeast surface display journal cover
BIOMIMETIC SYNTHESIS OF NATURAL PRODUCTS
Nature not only provides small molecules to modulate protein function but also provides clues on
efficient methods of constructing (biosynthesising) small molecules. Applying these principles to
ageladine A, we developed a 3-step synthesis of this compact natural product that was highlighted in C&E
News and was much shorter than an 11-step synthesis published in the same year. Projects include:
• biomimetic and semi-synthesis of natural products andanalogues
• the application of multicomponent reactions in the synthesis of marine natural products
• development of new organic reactions based on biomimetic chemistry
20 Department of Molecular Sciences2021/2022
CHEMICAL BIOLOGY AND DRUG DISCOVERY
FLUORESCENT TECHNOLOGIES BASED ON NATURAL PRODUCTS
Discoveries in my group resulted in the commercialisation of a fluorescent natural product
(epicocconone) and the establishment of my foirst spin-off company (Fluorotechnics) that listed on the
Aust. Stock Exchange in 2008. We have also discovered other new highly-fluorescent natural products
from marine sponges, microbes and plants. Projects in this area all involve commercially-relevant
research to address specific needs in medicine, biotechnology and research where tailored fluorophores
can improve current techniques or open the door on completely new areas. Projects include:
• discovery of new fluorescent natural products from marine sponges;
• synthesis of analogues of the fluorescent natural products such as ageladine A and epicocconone;
• synthesis of analogues of the GFP chromophore with dualemission;
• design and computational chemistry of novel fluorescentprobes.
The last project includes suicide turn-on or switchable fluorophores that can be used to covalently label
specific enzyme types and used to visualise the location of the enzymes inside cells and then use the
fluorophore as a mass tag to identify the exact protein modified using MALDI mass imaging and standard
proteomics techniques.
Epicocconone
Selected Publications
1. Chatterjee, S. Ahire, K., Karuso, P (2020) “Room-Temperature Dual Fluorescence of a Locked Green Fluorescent Protein Chromophore
Analogue” J. Am. Chem. Soc., 142, 738-49.
2. Gotsbacher, M. P., Cho, S. M., Kim, N. H., Liu, F., Kwon, H. J., Karuso, P. (2019) "Reverse chemical proteomics identifies an unanticipated
human target of the antimalarial artesunate" ACS Chem. Biol., 14, 636-43. [IF 4.4, Cit] (cover)
3. Ragini, K., Piggott, A. M. Karuso, P. (2019) “Bisindole Alkaloids from a New Zealand Deep-sea Marine Sponge Lamellomorpha strongylata”
Mar. Drugs, 17, 683; doi:10.3390/md17120683.
4. Liu, M., P. Karuso, Y. Feng, E. Kellenberger, F. Liu, C. Wang and R. J. Quinn (2019). “Is it time for artificial intelligence to predict the function
of natural products based on 2D-structure” MedChemComm 10, 1667-1677. [IF 2.4, Cit] (cover)
5. Karuso, P., Kum Cheung, W. L., Peixoto, P. A., Boulange, A. and Franck, X. (2017) “Epicocconone-Hemicyanine Hybrids: Near Infrared
Fluorophores for Protein Staining and Cell Imaging” Chem. - Eur. J., 23(8), 1820-1829. (cover)
6. Chand, S. and Karuso, P. (2017) “Isolation and total synthesis of two novel metabolites from the fissurellid mollusc Scutus antipodes”
Tetrahedron Lett., 58(10), 1020-1023.
7. Piggott, A.M. and Karuso, P. (2016) “Identifying the cellular targets of natural products using T7 phage display”, Nat. Prod. Rep., 33, 626-36.
8. Peixoto, P. A., Boulange, A., Ball, M., Naudin, M., Alle, T., Cosette, P., Karuso, P., Franck, X. (2014) “Design and synthesis of epicocconone
analogues with improved fluorescence properties”, J. Am. Chem. Soc. 136, 15248-56.
9. Karuso, P., “Modern methods for the isolation of natural product receptors” in Comprehensive Natural Products Chemistry II
Mander, L., Lui, H.-W. (Eds), Elsevier, Oxford, 2010, Vol. 9, pp513–67.
10. Shengule, S., and Karuso, P. (2006) “Concise synthesis of the marine natural product ageladine A” Org. Lett., 8, 4803-4.
11. Bell, P. J. L. and Karuso, P. (2003) “Epicocconone, a novel fluorescent compound from the fungus Epicoccum nigrum”, J. Am. Chem. Soc., 125,
9304-9305.
12. Shengule, S. R., Loa-Kum-Cheung, W., Parish, C., Blairvacq, M., Meijer, L., Nakao, Y. and Karuso, P. (2011) “A one-pot synthesis and
biological activity of ageladine A and analogues” J. Med. Chem. 54, 2492–503.
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