
Overview
Background
I completed my PhD in 2013 and I am currently a Senior Research Fellow and the Managing Director of the Soils of Science (S4S) Program at the University of Queensland. I am recognised as an emerging leader in antibiotic biodiscovery research. I have multidisciplinary research skills and expertise spanning the fields of organic chemistry and microbiology. I have made a significant contribution to the field of microbial biodiscovery employing high-throughput, high efficiency, natural product discovery to explore the chemical and biological properties of natural products produced by Australian marine and terrestrial microbes. I have identified and evaluated >40 new drugs targeting infectious diseases that attracted >$3M in research funding. I have led multi-year projects with industry, targeting animal health (ELANCO) and crop (NEXGEN Plants) and microbial chemical diversity (Microbial Screening Technologies; BioAustralis). I am a co-inventor on a UQ pending patent application documenting a new soil microbiome-inspired crop protection agent. This invention has attracted industry investment (NEXGEN Plants), to establish its potential, ahead of licensing and commercialisation. Therefore, I have co-led a project with industrial partner NEXGEN Plants, to investigate a new natural product that activates innate plant immunity defences against significant pathogens (patent pending). Since 2015, I have established the antibiotic biodiscovery capability at IMB targeting multidrug resistant (MDR) human pathogens and developed new approaches that have had significant knowledge impact in the antibiotic development and host defence research areas directed to combat MDR pathogens. This has resulted in the establishment of the Biodiscovery@UQ facility, a university-wide networking initiative designed to support excellence in biodiscovery research across UQ. I have secured funding from UQ to develop a new antitubercular drug lead (CIA), an ARC Linkage grant (LP19, CIB) to develop new anthelmintics and a grant from the University de La Frontera (collaborator), Chile to discover new antibiotics from Antarctic microbes, Marine CRC fund (CIA) to map the chemical diversity in Australian marine microbes and ARC LIEF grant. I co-led THE FIRST citizen science initiative, S4S, including developing the APP, website and running regional public workshops, with the aim of increasing public awareness about the role of soil microbes in antibiotic discovery. This initiative has attracted ~$1M in institutional and philanthropic support.
Availability
- Dr Zeinab Khalil is:
- Available for supervision
- Media expert
Qualifications
- Bachelor (Honours) of Pharmaceutical Sciences, Helwan University
- Masters (Research) of Microbiology, Helwan University
- Doctor of Philosophy, The University of Queensland
Research interests
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Cultivation Profiling (MATRIX)
An innovative high throughput miniaturized 24-well plate technology for the analytical cultivation of fungi and bacteria (MATRIX), supportive of multiple culture media and additive conditions, under broth static, broth shaken and solid phase. The MATRIX greatly accelerates, lowers the cost and increases the productivity of our microbial biodiscovery research.
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Chemical Profiling (UPLC-QTOF and GNPS)
An in situ MATRIX extraction to support rapid UPLC-DAD and UPLC-QTOF (MS/MS) profiling of crude extracts (and chromatographic fractions and pure metabolites), and data visualisation using global natural products social networking (GNPS) protocols. This greatly enhances our capacity to (i) assess chemical diversity in crude extracts/fractions, (ii) detect new from known, rare from common, and related from unrelated natural products, and (iii) detect transcriptional activation of silent biosynthetic gene clusters.
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Nitric oxide mediated transcriptional activation (NOMETA)
The use of nitric oxide as a transcriptional activator of silent biosynthetic gene clusters (BGCs) that code for bacterial and fungal defensive chemistry, including new classes of antibiotic and antiparasitic. This process allows for the addition of either (a) very low (sub nM) levels of Gram –ve bacteria lipopolysaccharide to fungal cultures to induce nitric oxide release, or (b) the direct addition of very low levels of an NO donor such as sodium nitric prusside to bacterial or fungal cultures, to induce the activation of silent BGCs encoded with microbial genomes.
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Microbial Biodiscovery and metabolite expression profiling
Many past studies into microbial secondary metabolism gene activation (autoregulators) have relied heavily on (i) the observation of morphological differentiation (which may or may not be linked to activation of new secondary metabolism), (ii) the up-regulation of a known metabolite/antibiotic(s) (which does not address the activation of silent “new” genes), or (iii) the appearance of pigmentation or antibiotic activity (which cannot differentiate new from old chemistry). A high throughput modern approach to the detection of gene activation events needs to rapidly and directly assess metabolite profiles. This project will develop and implement innovative methodologies and protocols for the HPLC-DAD-ELSD-HRMS analysis of >1M microbial metabolites – characterized by retention time, UV-vis spectrum and MW plus elemental composition. These analyses will be facilitated by the use of semi-automated and automated systems, including data archival and profiling software, to annotate, compare and evaluate similarities and differences in metabolite expression. This innovation implements a high throughput approach to detecting gene activation events by directly observing and providing a qualitative and quantitative assessment of microbial secondary metabolite production. This approach can be used to (i) detect, (ii) guide the isolation of, and (iii) evaluate the impact of, new gene activators, and their activated gene products.
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Gene activators
Whereas most microbial biodiscovery seeks to isolate new bioactive secondary metabolites produced under standard fermentation conditions, this project is innovative in that it seeks to challenge the microbial genome and activate otherwise silent secondary metabolite gene clusters. While this project will undoubtedly discover new microbial secondary metabolites, the main objective of the project is to discover and evaluate microbial metabolites that activate secondary metabolism – gene activators. This innovation addresses the unmet need to discover gene activators and assess their value in both basic science - as molecular probes to better understand microbial genomics and systems biology - as well as applied science – as molecular reagents to switch on “silent” microbial secondary metabolite gene clusters.
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Antibiotic and Cytotoxicity Profiling
Quantitative antibiotic screening against multiple Gram +ve and –ve bacteria, and fungi, including multidrug resistant clinical isolates such as methicillin resistant Staphylococcus aureus and Mycobacterium tuberculosis, as well as cytotoxicity screening against multiple mammalian (human) cancerous and non-cancerous cell lines, including multidrug resistant cancer cells over-expressing ABC transporter efflux pumps. This screening allows us to rapidly assemble a bioactivity profile on all prospective extracts.
Research impacts
In 2019, > 1.2 M people worldwide died from multidrug resistant (MDR) bacterial infections due to the lack of effective antibiotics, and we are in desperate need of chemical inspiration, to replenish the antibiotic pipeline. Our Antimicrobial Research and Development program has contributed significant NEW KNOWLEDGE through applying medicinal chemistry to the discovery of translational solutions to antimicrobial resistance (>100 new antibiotics) as well as novel basic research tools to help better understand the interactions between antibiotics and resistant bacteria. Specifically, our program has applied novel transcriptomics approaches to identify and activate silent genes within the microbial genome that informed the development of effective antibiotics.
Works
Search Professor Zeinab Khalil’s works on UQ eSpace
2014
Journal Article
Heronapyrrole D: a case of co-inspiration of natural product biosynthesis, total synthesis and biodiscovery
Schmidt, Jens, Khalil, Zeinab, Capon, Robert J. and Stark, Christian B. W. (2014). Heronapyrrole D: a case of co-inspiration of natural product biosynthesis, total synthesis and biodiscovery. Beilstein Journal of Organic Chemistry, 10 (1), 1228-1232. doi: 10.3762/bjoc.10.121
2014
Journal Article
Mollemycin A: an antimalarial and antibacterial glyco-hexadepsipeptide-polyketide from an Australian marine-derived Streptomyces sp. (CMB-M0244)
Raju, Ritesh, Khalil, Zeinab G., Piggott, Andrew M., Blumenthal, Antje, Gardiner, Donald L., Skinner-Adams, Tina S. and Capon, Robert J. (2014). Mollemycin A: an antimalarial and antibacterial glyco-hexadepsipeptide-polyketide from an Australian marine-derived Streptomyces sp. (CMB-M0244). Organic Letters, 16 (6), 1716-1719. doi: 10.1021/ol5003913
2014
Journal Article
Callyspongisines A-D: Bromopyrrole alkaloids from an Australian marine sponge, Callyspongia sp.
Plisson,Fabien, Prasad, Pritesh, Xiao, Xue, Piggott, Andrew M., Huang, Xiao-cong, Khalil, Zeinab and Capon, Robert J. (2014). Callyspongisines A-D: Bromopyrrole alkaloids from an Australian marine sponge, Callyspongia sp.. Organic and Biomolecular Chemistry, 12 (10), 1579-1584. doi: 10.1039/c4ob00091a
2014
Journal Article
Lipopolysaccharide (LPS) stimulation of fungal secondary metabolism
Khalil, Zeinab G., Kalansuriya, Pabasara and Capon, Robert J. (2014). Lipopolysaccharide (LPS) stimulation of fungal secondary metabolism. Mycology, 5 (3), 168-178. doi: 10.1080/21501203.2014.930530
2013
Other Outputs
Innovations in Microbial Biodiscovery, Targeting Silent Metabolism and New Chemical Diversity
Khalil, Zeinab (2013). Innovations in Microbial Biodiscovery, Targeting Silent Metabolism and New Chemical Diversity. PhD Thesis, Institute for Molecular Bioscience, The University of Queensland. doi: 10.14264/uql.2017.734
2012
Journal Article
Structural and stereochemical investigations into bromotyrosine-derived metabolites from southern Australian marine sponges, Pseudoceratina spp.
Salim, Angela A., Khalil, Zeinab G. and Capon, Robert J. (2012). Structural and stereochemical investigations into bromotyrosine-derived metabolites from southern Australian marine sponges, Pseudoceratina spp.. Tetrahedron, 68 (47), 9802-9807. doi: 10.1016/j.tet.2012.09.008
2012
Journal Article
A search for kinase inhibitors and antibacterial agents: bromopyrrolo-2-aminoimidazoles from a deep-water Great Australian Bight sponge, Axinella sp.
Zhang, Hua, Khalil, Zeinab, Conte, Melissa M., Plisson, Fabien and Capon, Robert J. (2012). A search for kinase inhibitors and antibacterial agents: bromopyrrolo-2-aminoimidazoles from a deep-water Great Australian Bight sponge, Axinella sp.. Tetrahedron Letters, 53 (29), 3784-3787. doi: 10.1016/j.tetlet.2012.05.051
2012
Journal Article
Kinase inhibitor scaffolds against neurodegenerative diseases from a southern Australian Ascidian, Didemnum sp.
Plisson, Fabien, Conte, Melissa, Khalil, Zeinab, Huang, Xiao-Cong, Piggott, Andrew M. and Capon, Robert J. (2012). Kinase inhibitor scaffolds against neurodegenerative diseases from a southern Australian Ascidian, Didemnum sp.. ChemMedChem, 7 (6), 983-990. doi: 10.1002/cmdc.201200169
2012
Journal Article
Lamellarins as inhibitors of P-glycoprotein-mediated multidrug resistance in a human colon cancer cell line
Plisson, Fabien, Huang, Xiao-Cong, Zhang, Hua, Khalil, Zeinab and Capon, Robert J. (2012). Lamellarins as inhibitors of P-glycoprotein-mediated multidrug resistance in a human colon cancer cell line. Chemistry - An Asian Journal, 7 (7), 1616-1623. doi: 10.1002/asia.201101049
2012
Journal Article
New dictyodendrins as BACE inhibitors from a southern Australian marine sponge, Ianthella sp.
Zhang, Hua, Conte, Melissa M., Khalil, Zeinab, Huang, Xiao-Cong and Capon, Robert J. (2012). New dictyodendrins as BACE inhibitors from a southern Australian marine sponge, Ianthella sp.. Rsc Advances, 2 (10), 4209-4214. doi: 10.1039/c2ra20322g
2012
Journal Article
A search for BACE inhibitors reveals new biosynthetically related pyrrolidones, furanones and pyrroles from a southern Australian marine sponge, Ianthella sp.
Zhang, Hua, Conte, Melissa M., Huang, Xiao-Cong, Khalil, Zeinab and Capon, Robert J. (2012). A search for BACE inhibitors reveals new biosynthetically related pyrrolidones, furanones and pyrroles from a southern Australian marine sponge, Ianthella sp.. Organic and Biomolecular Chemistry, 10 (13), 2656-2663. doi: 10.1039/c2ob06747a
2012
Journal Article
Heronamycin A: A new benzothiazine ansamycin from an Australian marine-derived Streptomyces sp.
Raju, Ritesh, Piggott, Andrew M., Khalil, Zeinab, Bernhardt, Paul V. and Capon, Robert J. (2012). Heronamycin A: A new benzothiazine ansamycin from an Australian marine-derived Streptomyces sp.. Tetrahedron Letters, 53 (9), 1063-1065. doi: 10.1016/j.tetlet.2011.12.064
2012
Journal Article
Spiralisones A-D: acylphloroglucinol hemiketals from an Australian marine brown alga, Zonaria spiralis
Zhang, Hua, Xiao, Xue, Conte, Melissa M., Khalil, Zeinab and Capon, Robert J. (2012). Spiralisones A-D: acylphloroglucinol hemiketals from an Australian marine brown alga, Zonaria spiralis. Organic and Biomolecular Chemistry, 10 (48), 9671-9676. doi: 10.1039/c2ob26988k
2011
Journal Article
Ikirydinium A: A new indole alkaloid from the seeds of Hunteria umbellata (K. Schum)
Ajala, Olusegun S., Piggott, Andrew M., Plisson, Fabien, Zeinab, Zeinab, Huang, Xiao-cong, Adesegun, Sunday A., Coker, Herbert A. B. and Capon, Robert J. (2011). Ikirydinium A: A new indole alkaloid from the seeds of Hunteria umbellata (K. Schum). Tetrahedron Letters, 52 (52), 7125-7127. doi: 10.1016/j.tetlet.2011.10.106
2011
Journal Article
Fascioquinols A-F: Bioactive meroterpenes from a deep-water southern Australian marine sponge, Fasciospongia sp
Zhang, Hua, Khalil, Zeinab G. and Capon, Robert J. (2011). Fascioquinols A-F: Bioactive meroterpenes from a deep-water southern Australian marine sponge, Fasciospongia sp. Tetrahedron, 67 (14), 2591-2595. doi: 10.1016/j.tet.2011.02.015
2011
Journal Article
Reveromycins revealed: New polyketide spiroketals from Australian marine-derived and terrestrial Streptomyces spp. A case of natural products vs artifacts
Fremlin, Leith, Farrugia, Michelle, Piggott, Andrew M., Khalil, Zeinab, Lacey, Ernest and Capon, Robert J. (2011). Reveromycins revealed: New polyketide spiroketals from Australian marine-derived and terrestrial Streptomyces spp. A case of natural products vs artifacts. Organic & Biomolecular Chemistry, 9 (4), 1201-1211. doi: 10.1039/c0ob00654h
2010
Journal Article
Heronapyrroles A-C: Farnesylated 2-nitropyrroles from an Australian marine-derived Streptomyces sp.
Raju, Ritesh, Piggott, Andrew M., Barrientos Diaz, Leticia X., Khalil, Zeinab and Capon, Robert J. (2010). Heronapyrroles A-C: Farnesylated 2-nitropyrroles from an Australian marine-derived Streptomyces sp.. Organic Letters, 12 (22), 5158-5161. doi: 10.1021/ol102162d
2010
Journal Article
Heterofibrins: Inhibitors of lipid droplet formation from a deep-water southern Australian marine sponge, Spongia (Heterofibria) sp.
Salim, Angela A., Rae, James, Fontaine, Frank, Conte, Melissa M., Khalil, Zeinab, Martin, Sally, Parton, Robert G. and Capon, Robert J. (2010). Heterofibrins: Inhibitors of lipid droplet formation from a deep-water southern Australian marine sponge, Spongia (Heterofibria) sp.. Organic and Biomolecular Chemistry, 8 (14), 3188-3194. doi: 10.1039/c003840g
2010
Journal Article
9-(5‘-Deoxy-5’-thio-β-d-xylofuranosyl)adenine disulfide from the Southern Australian marine sponge trachycladus laevispirulifer: The first natural occurrence of a nucleoside disulfide
Peng, Chongsheng, Gunaherath, G. M. Kamal B., Piggott, Andrew M., Khalil, Zeinab, Conte, Melissa and Capon, Robert J. (2010). 9-(5‘-Deoxy-5’-thio-β-d-xylofuranosyl)adenine disulfide from the Southern Australian marine sponge trachycladus laevispirulifer: The first natural occurrence of a nucleoside disulfide. Australian Journal of Chemistry, 63 (6), 873-876. doi: 10.1071/CH09645
Funding
Current funding
Past funding
Supervision
Availability
- Dr Zeinab Khalil is:
- Available for supervision
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Available projects
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Mapping chemical diversity in Australian marine microbes
This project seeks to develop advanced and optimised methods in UPLC-QTOF-MS/MS molecular networking, to rapidly, cost effectively, reproducibly and quantitatively map the small molecule and peptide chemical diversity of taxonomically and geographically diverse Australian marine microbes and microalgae, including fresh and processed biomass, biorefinery fractions and outputs, and formulated marine bioproducts – to advance the discovery and development of valuable new marine bioproducts.
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Soils for Science
Soils for Science (S4S) seeks to build a partnership between UQ researchers and the public, to fast-track the discovery of new antibiotics. S4S will engage pastoralists, farmers, homeowners, schools and others, to assemble a collection of 100,000 Australian soil samples, from which we will recover a living library of >2,000,000 microbes (bacteria and fungi) rich in new antibiotics, including against important crop pathogens.
This project seeks to discover the next generation of new antibiotics against multi-drug resistant pathogens.
Supervision history
Current supervision
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Doctor Philosophy
Towards the sustainable discovery and development of new antibiotics
Principal Advisor
Other advisors: Dr Angela Salim, Professor Rob Capon
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Doctor Philosophy
Production of the Mannopeptimycin Antibiotic and other unknown Biosynthetic Gene Clusters from Streptomyces hygroscopicus
Associate Advisor
Other advisors: Professor Esteban Marcellin
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Doctor Philosophy
New antiparasitics to protect Australian livestock
Associate Advisor
Other advisors: Professor Rob Capon
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Doctor Philosophy
Medicinal chemistry of new Nature-inspired treatments for Inflammatory Bowel Disease (IBD)
Associate Advisor
Other advisors: Dr Angela Salim, Associate Professor Jakob Begun, Professor Rob Capon
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Doctor Philosophy
Upconversion-encoded microspheres for glucocorticoids detection as food hazards or health markers
Associate Advisor
Other advisors: Dr Kayvan Etebari, Dr Run Zhang, Professor Yasmina Sultanbawa
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Master Philosophy
Exploring Australian Marine Microbial Bioresources for Novel Therapeutic Agent
Associate Advisor
Other advisors: Professor Rob Capon, Dr Angela Salim
Completed supervision
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2024
Doctor Philosophy
Production of the Mannopeptimycin Antibiotic and Other Unknown Biosynthetic Gene Clusters from Streptomyces hygroscopicus
Associate Advisor
Other advisors: Professor Esteban Marcellin
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2023
Doctor Philosophy
Applying Advanced Molecular Networking Techniques to Explore Chemical Diversity of Australian Microbes
Associate Advisor
Other advisors: Professor Rob Capon
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2023
Doctor Philosophy
Microbial biodiscovery from Australian marine-derived and Venezuelan quartz-rich cave-derived microorganisms.
Associate Advisor
Other advisors: Professor Rob Capon
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2022
Doctor Philosophy
Microbial Biodiversity: Expanding acess to microbial chemical diversity using new techniques
Associate Advisor
Other advisors: Professor Rob Capon
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2021
Doctor Philosophy
Microbial Biodiversity: Exploring Australian Microbial Natural Products
Associate Advisor
Other advisors: Professor Rob Capon
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2019
Doctor Philosophy
Fungal Biodiscovery: Strategies to Explore Fungal Secondary Metabolite Potential
Associate Advisor
Other advisors: Professor Rob Capon
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2019
Doctor Philosophy
Exploring the Natural Products of Australian Sheep Coprophilous Fungi
Associate Advisor
Other advisors: Professor Rob Capon
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2019
Doctor Philosophy
Adventures in Australian Microbial Biodiscovery
Associate Advisor
Other advisors: Professor Rob Capon
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2016
Doctor Philosophy
Microbial Chemical Diversity: Strategies to Stimulate Microbial Secondary Metabolite Potential
Associate Advisor
Other advisors: Professor Rob Capon
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2016
Doctor Philosophy
Biodiscovery of Plant Growth-Promoting Rhizobacteria (PGPR) and their role in plant-microbe interactions
Associate Advisor
Other advisors: Professor Rob Capon, Dr Lilia Carvalhais
Media
Enquiries
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- Antibiotics biodiscovery
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