Molecular Sciences Research Booklet 2021/2022 - Macquarie University

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Molecular Sciences Research Booklet 2021/2022 - Macquarie University
    Faculty of Science and Engineering

    Molecular Sciences
    Research Booklet

epartment of Chemistry and Biomolecular Sciences   1
Molecular Sciences Research Booklet 2021/2022 - Macquarie University

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

Macquarie University NSW 2109 Australia
T: +61 (2) 9850 8275
CRICOS Provider 00002J

2                                                                 Department of Molecular Sciences
Molecular Sciences Research Booklet 2021/2022 - Macquarie University

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
Molecular Sciences Research Booklet 2021/2022 - Macquarie University

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
Molecular Sciences Research Booklet 2021/2022 - Macquarie University

    Department of Molecular Sciences   5
Molecular Sciences Research Booklet 2021/2022 - Macquarie University

                                           Associate Professor Louise Brown
                                           Room: 6WW 305 T: (02) 9850 8294


                     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.

                     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
Molecular Sciences Research Booklet 2021/2022 - Macquarie University

                                                                                                                                   STRUCTURAL BIOLOGY

                                                           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
                                                           This research has strong links with industry and is funded by
      Figure 4: Engineering of bacteria for bio-hydrogen   an ARENA renewable energy grant.

           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
Molecular Sciences Research Booklet 2021/2022 - Macquarie University

                                     Dr Amy K. Cain
                                     Room: 6WW208 T: (02) 9850 8206


                    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.

                    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.

                    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
Molecular Sciences Research Booklet 2021/2022 - Macquarie University

                                                                                                                         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.

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,
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,
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
Molecular Sciences Research Booklet 2021/2022 - Macquarie University

                                                Dr Alfonso Garcia-Bennett
                                                Room: 4WW337 T: (02) 9850 8285


                              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.

                              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
                                                                 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.

                              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 Sciences

                                                                                                                              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 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                                                                                         11

                                                          Professor Paul A. Haynes
                                                          Room: 6WW309 T: (02) 9850 6258


                                         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
                                         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 Sciences

                                                                                                                       PLANT AND 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                                                                              13

                                                                             Dr Ian Jamie
                                                                             Room: 4WW236 T: (02) 9850 8293


                                                            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
                                                                                We are also interested in how fruit flies react to odours
                                                                     N          produced by bacteria, as some bacteria are pathogens, some

                                                                                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.
                                                            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 (, 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 Sciences

                                                                                                                                          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.
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.


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”,, 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.
Department of Molecular Sciences                                                                                                   15

                                                                             Associate Professor Joanne Jamie
                                                                             Room: 4WW231 T : ( 0 2 ) 9850 8283


                                                           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

                                                           16                                                                              Department of Molecular Sciences

                                                                                                                                 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.

                          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                                                                                          17

                                       Dr Paul Jaschke
                                       Room: 14EAR357 T: (02) 9850 8295


                    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


                    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 Sciences

                                                                                                                             SYNTHETIC BIOLOGY

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.


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:

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

Department of Molecular Sciences                                                                                        19
                                                     Professor Peter Karuso

                                                     Room: 4WW232 T: (02) 9850 8290

                                      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

                                                      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 Sciences

                                                                                                                                                           CHEMICAL BIOLOGY AND DRUG DISCOVERY
  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.


 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,
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.

 Department of Molecular Sciences                                                                                                                  21
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