Dr Zeinab Khalil

Research Fellow

Institute for Molecular Bioscience
z.khalil@uq.edu.au
+61 7 334 62980

Overview

Dr Khalil was awarded a competitive MSc scholarship in October 2003 by School of Pharmacy, Cairo, Egypt to pursue her studies at the Department of Microbiology and Immunology, developing rapid detection techniques for Gram-negative and Gram-positive infections using nitrate reductase. Following her MSc degree, she was awarded UQ scholarship and commenced her PhD studies under the supervision of Prof Capon, at the UQ Institute for Molecular Biosciences (IMB). In 2013 she was awarded a PhD, with a thesis titled “Innovations in microbial biodiscovery, targeting silent metabolism and new chemical diversity”. In 2013-2014 she held a research position on a UQ-industry (Progenra Inc, USA) funded project targeting the discovery of new ubiquitin ligase inhibitors for the treatment of severe neurodegenerative diseases. In 2014-2016 she held a research position on a UQ-industry funded project targeting the discovery of new anthelmintics from microbes for the treatment of gastrointestinal infections (Haemonchus contortus). In 2016-2019, and building on a discovery made during her PhD, she took up a postdoctoral position in a joint project between the UQ Institute for Molecular Bioscience (Prof Capon) and the UQ Diamantina Institute (Assoc. Prof. Blumenthal), funded by an Australian Tropical Medicines Commercialisation (ATMC) grant, to develop new antitubercular agents from Australian microbes. In 2019 this position transitioned to a UQ-US Department of Defence funded project, further advancing the wollamides, a new class of antitubercular antibiotic. In 2019 she joined a UQ-industry (Nexgen Plants) funded project, to develop a non-cytotoxic bacterial natural product, co-discovered by Dr Khalil and Prof. Capon that stimulates a natural immune response in plants, protecting them from pathogen infection (i.e., Phytophthora). This technology has been disclosed to the UQ commercialisation company UniQuest.

Research Interests

  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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

Prior to our research group, the chemistry and microbiology fields had limited understanding of the silent biosynthetic gene clusters (BGCs) in the microbial genome. Our research paved the way to up-regulate the production of novel antibiotics, evaluate their antimicrobial properties and track their mechanism of action

Dr Khalil research has resulted in significant contributions to the fields of microbiology, natural products chemistry, genomics and antibiotic biodiscovery. Dr Khalil implemented an innovative new strategy for studying the role of nitric oxide (NO) as a transcriptional regulator to activate silent microbial biosynthetic gene clusters (BGCs) for antibiotic expression.

Antibiotic Biodiscovery: Dr Khalil independently established the Capon group facility for screening against multidrug resistant (MDR) clinical isolates, where she played a key role in discovering a new class of antibiotic that has already attracted >$2M in research funding to UQ.

Microbial Biodiscovery: Dr Khalil developed a new approach to enrich the microbial biodiscovery pipeline with novel metabolites that possess noteworthy biological activities as antibiotics (against MDR Gram-negative and Gram-positive bacteria) and anticancer. She developed new methods that have had significant knowledge impact in the antibiotic development and host defence research areas directed to combat MDR pathogens.

A major highlight of Dr Khalil's research has been the discovery and development of a new class of Streptomyces cyclic hexapeptide, wollamides, with excellent activity against pathogenic mycobacteria. This research was published in a first-authored paper in the Nature Index ranked journal and was subsequently highlighted by ‘Hot off the press’ in an equally high impact journal, Natural Products Reports. Dr Khalil's impact in chemistry, microbiology and genomics have been leveraged within the research team in UQ and at other research institutes (Boston University).

Qualifications

  • Doctor of Philosophy, The University of Queensland
  • Master of Microbiology, Helwan University
  • Bachelor of Pharmaceutical Sciences (Hons), Helwyn University

Publications

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Grants

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Supervision

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Publications

Book Chapter

Journal Article

Conference Publication

Other Outputs

Grants (Administered at UQ)

PhD and MPhil Supervision

Current Supervision

  • Doctor Philosophy — Associate Advisor

    Other advisors:

  • Doctor Philosophy — Associate Advisor

    Other advisors:

  • Doctor Philosophy — Associate Advisor

    Other advisors:

  • Doctor Philosophy — Associate Advisor

Completed Supervision