
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
2021
Journal Article
Precursor-directed biosynthesis mediated amplification of minor aza phenylpropanoid piperazines in an Australian marine fish-gut-derived fungus, Chrysosporium sp. CMB-F214
Elbanna, Ahmed H., Agampodi Dewa, Amila, Khalil, Zeinab G. and Capon, Robert J. (2021). Precursor-directed biosynthesis mediated amplification of minor aza phenylpropanoid piperazines in an Australian marine fish-gut-derived fungus, Chrysosporium sp. CMB-F214. Marine Drugs, 19 (9) 478, 1-15. doi: 10.3390/md19090478
2021
Journal Article
Poly(hydrophobic amino acid) conjugates for the delivery of multiepitope vaccine against Group A Streptococcus
Azuar, Armira, Shibu, Mohini A., Adilbish, Nomin, Marasini, Nirmal, Hung, Hong, Yang, Jieru, Luo, Yacheng, Khalil, Zeinab G., Capon, Robert J., Hussein, Waleed M., Toth, Istvan and Skwarczynski, Mariusz (2021). Poly(hydrophobic amino acid) conjugates for the delivery of multiepitope vaccine against Group A Streptococcus. Bioconjugate Chemistry, 32 (11) acs.bioconjchem.1c00333, 2307-2317. doi: 10.1021/acs.bioconjchem.1c00333
2021
Journal Article
Polyethylenimine quantity and molecular weight influence its adjuvanting properties in liposomal peptide vaccines
Dai, Charles C., Huang, Wenbin, Yang, Jieru, Hussein, Waleed M., Wang, Jingwen, Khalil, Zeinab G., Capon, Robert J., Toth, Istvan and Stephenson, Rachel J. (2021). Polyethylenimine quantity and molecular weight influence its adjuvanting properties in liposomal peptide vaccines. Bioorganic and Medicinal Chemistry Letters, 40 127920, 1-7. doi: 10.1016/j.bmcl.2021.127920
2021
Journal Article
Cell-penetrating peptides-based liposomal delivery system enhanced immunogenicity of peptide-based vaccine against group A streptococcus
Yang, Jieru, Firdaus, Farrhana, Azuar, Armira, Khalil, Zeinab G., Marasini, Nirmal, Capon, Robert J., Hussein, Waleed M., Toth, Istvan and Skwarczynski, Mariusz (2021). Cell-penetrating peptides-based liposomal delivery system enhanced immunogenicity of peptide-based vaccine against group A streptococcus. Vaccines, 9 (5) 499, 499. doi: 10.3390/vaccines9050499
2021
Journal Article
N-amino-L-proline methyl ester from an Australian fish gut-derived fungus: challenging the distinction between natural product and artifact
Mohamed, Osama G., Khalil, Zeinab G. and Capon, Robert J. (2021). N-amino-L-proline methyl ester from an Australian fish gut-derived fungus: challenging the distinction between natural product and artifact. Marine Drugs, 19 (3) 151, 1-14. doi: 10.3390/md19030151
2021
Journal Article
Neobulgarones revisited: anti and syn bianthrones from an Australian mud dauber wasp nest-associated fungus, Penicillium sp. CMB-MD22
Elbanna, Ahmed H., Khalil, Zeinab G., Bernhardt, Paul V. and Capon, Robert J. (2021). Neobulgarones revisited: anti and syn bianthrones from an Australian mud dauber wasp nest-associated fungus, Penicillium sp. CMB-MD22. Journal of Natural Products, 84 (3) acs.jnatprod.0c01035, 762-770. doi: 10.1021/acs.jnatprod.0c01035
2021
Journal Article
Immunogenicity assessment of cell wall carbohydrates of Group A Streptococcus via self-adjuvanted glyco-lipopeptides
Khatun, Farjana, Dai, Charles C., Rivera-Hernandez, Tania, Hussein, Waleed M., Khalil, Zeinab G., Capon, Robert J., Toth, Istvan and Stephenson, Rachel J. (2021). Immunogenicity assessment of cell wall carbohydrates of Group A Streptococcus via self-adjuvanted glyco-lipopeptides. ACS Infectious Diseases, 7 (2) acsinfecdis.0c00722, 390-405. doi: 10.1021/acsinfecdis.0c00722
2021
Journal Article
Poly(hydrophobic amino acid)-based self-adjuvanting nanoparticles for Group A Streptococcus vaccine delivery
Azuar, Armira, Li, Zhuoqing, Shibu, Mohini A., Zhao, Lili, Luo, Yacheng, Shalash, Ahmed O., Khalil, Zeinab G., Capon, Robert J., Hussein, Waleed M., Toth, Istvan and Skwarczynski, Mariusz (2021). Poly(hydrophobic amino acid)-based self-adjuvanting nanoparticles for Group A Streptococcus vaccine delivery. Journal of Medicinal Chemistry, 64 (5) acs.jmedchem.0c01660, 2648-2658. doi: 10.1021/acs.jmedchem.0c01660
2020
Journal Article
A dual-adjuvanting strategy for peptide-based subunit vaccines against group A Streptococcus: lipidation and polyelectrolyte complexes
Zhao, Lili, Yang, Jieru, Nahar, Ummey Jannatun, Khalil, Zeinab G., Capon, Robert J., Hussein, Waleed M., Skwarczynski, Mariusz and Toth, Istvan (2020). A dual-adjuvanting strategy for peptide-based subunit vaccines against group A Streptococcus: lipidation and polyelectrolyte complexes. Bioorganic and Medicinal Chemistry, 28 (24) 115823, 115823. doi: 10.1016/j.bmc.2020.115823
2020
Journal Article
Lincolnenins A–D: isomeric bactericidal bianthracenes from Streptomyces lincolnensis
Mohamed, Osama G., Khalil, Zeinab G., Salim, Angela A., Cui, Hui, Blumenthal, Antje and Capon, Robert J. (2020). Lincolnenins A–D: isomeric bactericidal bianthracenes from Streptomyces lincolnensis. The Journal of Organic Chemistry, 86 (16) acs.joc.0c02492, 11011-11018. doi: 10.1021/acs.joc.0c02492
2020
Journal Article
Polyethylenimine: an intranasal adjuvant for liposomal peptide-based subunit vaccine against Group A Streptococcus
Dai, Charles C., Yang, Jieru, Hussein, Waleed M., Zhao, Lili, Wang, Xiumin, Khalil, Zeinab G., Capon, Robert J., Toth, Istvan and Stephenson, Rachel J. (2020). Polyethylenimine: an intranasal adjuvant for liposomal peptide-based subunit vaccine against Group A Streptococcus. ACS Infectious Diseases, 6 (9) acsinfecdis.0c00452, 2502-2512. doi: 10.1021/acsinfecdis.0c00452
2020
Journal Article
Exploring natural product artifacts: the polyketide enterocin warms to a ballet of isomers
Salim, Angela A., Samarasekera, Kaumadi, Khalil, Zeinab G. and Capon, Robert J. (2020). Exploring natural product artifacts: the polyketide enterocin warms to a ballet of isomers. Organic Letters, 22 (12) acs.orglett.0c01629, 4828-4832. doi: 10.1021/acs.orglett.0c01629
2020
Journal Article
Levoglucosenone and its Pseudoenantiomer iso-Levoglucosenone as scaffolds for drug discovery and development
Liu, Xin, Carr, Paul, Gardiner, Michael G., Banwell, Martin G., Elbanna, Ahmed H., Khalil, Zeinab G. and Capon, Robert J. (2020). Levoglucosenone and its Pseudoenantiomer iso-Levoglucosenone as scaffolds for drug discovery and development. ACS Omega, 5 (23) acsomega.0c01331, 13926-13939. doi: 10.1021/acsomega.0c01331
2020
Journal Article
Opsonic activity of conservative versus variable regions of the Group A Streptococcus M protein
Dai, Chuankai, Khalil, Zeinab G., Hussein, Waleed M., Yang, Jieru, Wang, Xiumin, Zhao, Lili, Capon, Robert J., Toth, Istvan and Stephenson, Rachel J. (2020). Opsonic activity of conservative versus variable regions of the Group A Streptococcus M protein. Vaccines, 8 (2) 210, 210. doi: 10.3390/vaccines8020210
2020
Journal Article
Structure–activity analysis of cyclic multicomponent lipopeptide self-adjuvanting vaccine candidates presenting Group A Streptococcus antigens
Madge, Harrison Y. R., Sharma, Hansa, Hussein, Waleed M., Khalil, Zeinab G., Capon, Robert John, Toth, Istvan and Stephenson, Rachel (2020). Structure–activity analysis of cyclic multicomponent lipopeptide self-adjuvanting vaccine candidates presenting Group A Streptococcus antigens. Journal of Medicinal Chemistry, 63 (10) acs.jmedchem.0c00203, 5387-5397. doi: 10.1021/acs.jmedchem.0c00203
2020
Journal Article
Genomic and metabolomic analysis of Antarctic bacteria revealed culture and elicitation conditions for the production of antimicrobial compounds
Núñez-Montero, Kattia, Quezada-Solís, Damián, Khalil, Zeinab G., Capon, Robert J., Andreote, Fernando D. and Barrientos, Leticia (2020). Genomic and metabolomic analysis of Antarctic bacteria revealed culture and elicitation conditions for the production of antimicrobial compounds. Biomolecules, 10 (5) 673, 673. doi: 10.3390/biom10050673
2020
Journal Article
Development of polyelectrolyte complexes for the delivery of peptide-based subunit vaccines against group A streptococcus
Zhao, Lili, Jin, Wanli, Cruz, Jazmina Gonzalez, Marasini, Nirmal, Khalil, Zeinab G., Capon, Robert J., Hussein, Waleed M., Skwarczynski, Mariusz and Toth, Istvan (2020). Development of polyelectrolyte complexes for the delivery of peptide-based subunit vaccines against group A streptococcus. Nanomaterials, 10 (5) 823, 823. doi: 10.3390/nano10050823
2020
Journal Article
Poly(amino acids) as a potent self-adjuvanting delivery system for peptide-based nanovaccines
Skwarczynski, Mariusz, Zhao, Guangzu, Boer, Jennifer C., Ozberk, Victoria, Azuar, Armira, Gonzalez Cruz, Jazmina, Kumar Giddam, Ashwini, Khalil, Zeinab G., Pandey, Manisha, Shibu, Mohini A., Hussein, Waleed M., Nevagi, Reshma J., Batzloff, Michael R., Wells, James W., Capon, Robert J., Plebanski, Magdalena, Good, Michael F. and Toth, Istvan (2020). Poly(amino acids) as a potent self-adjuvanting delivery system for peptide-based nanovaccines. Science Advances, 6 (5) eaax2285, eaax2285. doi: 10.1126/sciadv.aax2285
2020
Journal Article
Chrysosporazines F–M: P-glycoprotein inhibitory phenylpropanoid piperazines from an Australian marine fish derived fungus, Chrysosporium sp. CMB-F294
Mohamed, Osama G., Salim, Angela A., Khalil, Zeinab G., Elbanna, Ahmed H., Bernhardt, Paul V. and Capon, Robert J. (2020). Chrysosporazines F–M: P-glycoprotein inhibitory phenylpropanoid piperazines from an Australian marine fish derived fungus, Chrysosporium sp. CMB-F294. Journal of Natural Products, 83 (2) acs.jnatprod.9b01181, 497-504. doi: 10.1021/acs.jnatprod.9b01181
2020
Journal Article
Polyacrylate–peptide antigen conjugate as a single-dose oral vaccine against Group A Streptococcus
Faruck, Mohammad Omer, Zhao, Lili, Hussein, Waleed M., Khalil, Zeinab G., Capon, Robert J., Skwarczynski, Mariusz and Toth, Istvan (2020). Polyacrylate–peptide antigen conjugate as a single-dose oral vaccine against Group A Streptococcus. Vaccines, 8 (1) 23, 1-10. doi: 10.3390/vaccines8010023
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
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
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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
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
Microbial biodiscovery from Australian marine-derived and Venezuelan quartz-rich cave-derived microorganisms.
Associate Advisor
Other advisors: Professor Rob Capon
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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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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
Exploring the Natural Products of Australian Sheep Coprophilous Fungi
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
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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