Velkov Lab research
Collaborations | Student research projects | Publications
About Professor Tony Velkov
One of the most outstanding accomplishments of modern medicine was the development of antibiotics for treatment of bacterial infections that were widely fatal. However, due to a marked decline in discovery of new antibiotics over the past few decades, the world is now facing an enormous threat from the emergence of bacteria that are resistant to all available antibiotics.
A/Prof Velkov is a world leading expert in several aspects of antibiotic pharmacology, including their mode of action, chemistry, structure-activity relationships and toxicity. He has extensive international industry experience, having been awarded two NHMRC industry fellowships and a REDI MPTConnect Industry Fellowship. He was recognised by the NHMRC with Excellence Awards in 2011 and again in 2015.
The significant impact of his anti-infective research was highlighted by the NHMRC through a ‘Ten of the Best’ award for his novel lipopeptide discovery project grant. He has a unique setup in his laboratory for developing novel lipopeptide and depsi-pepetide antibiotics targeting multi-resistant superbugs (from drug design, chemistry synthesis, in vitro models to in vivo safety and efficacy evaluations). A/Prof Velkov has published >240 papers on antibiotic drug discovery, PK/PD, pharmacology and resistance. He is a key opinion leader in the field and has served on Editorial boards (e.g. Br J Pharmacol) and an invited reviewer for prominent international journals (e.g. Nat Med).
He is a serving member of several professional societies, including American Society for Microbiology, Australian Society for Biochemistry and Molecular Biology, Australian Pharmaceutical Science Association, and Australian Thoracic Society. A/Prof Velkov serves as a regular reviewer of grant applications for various government bodies including the National Health and Medical Research Council, Australian Research Council, New Zealand Marsden Fund, the European Society of Clinical Microbiology and Infectious Diseases, Wellcome Trust (UK), Research Councils UK (RCUK), the Netherlands Organisation for Scientific Research, French National Research Agency and Israel Science Foundation.
A/Prof Velkov has a proven track record in undergraduate and postgraduate teaching and is strongly committed to supporting postgraduate education within the university. He has a substantial record of successful higher degree by research completions as primary supervisor (16 PhD, 15 Masters and 10 Honors students). His internationally leading research is underpinned by an exceptional track record in advancing projects to clinical development and commercialisation of intellectual property through his extensive academic-industry partnerships.
A/Prof Velkov’s international leadership is also demonstrated by significant continuous funding support from major Australian and international granting bodies. His innovative research is encompassed by complementary and integrated streams that encompass the ‘lab bench to bedside’ doctrine and efficiently translate his multidisciplinary research to clinical practice and pharmaceutical products.
Our research
Current projects
- Development of novel teixobactin-lipopeptide hybrid antibiotics
- Function and biosynthetic origin of octapeptin antibiotics
- Pharmacology and neurotoxicity of CNS polymyxins
- Systems pharmacology of novel Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) modulator/corrector drugs
Visit Professor Tony Velkov's Monash research profile to see a full listing of current projects.
Research activities
My internationally leading anti-infective pharmacology research programs are underpinned by an exceptional track record in intellectual property development, commercialisation, strong multidisciplinary collaborations and industry engagement. My team has extensive funding from the US National Institute of Health and US Department of Defence, NHMRC, ARC and MPTConnect. My innovative research involves complementary and integrated streams that encompass the ‘lab bench to bedside’ doctrine and efficiently translate my multidisciplinary research to clinical practice and products. Importantly, my research targets a global health crisis, the lack of new antibiotics in a ‘Bad Bugs, No Drugs’ era.
My four major research programs are:
(1) Development of novel teixobactin-lipopeptide hybrid antibiotics
Teixobactins are a recently discovered novel antibiotic class that typically possess a narrow spectrum of activity against Gram-positive bacteria. The most notable property of teixobactin is that it is the first and only resistance-resistant antibiotic. A/Prof Velkov’s sixth research tier focuses on the discovery of novel teixobactin-lipopeptide hybrids for the treatment of pan-drug resistant (PDR) lung infections. Excitingly, his team has developed novel hybrids that are superior to the native teixobactin compound as they retain this key property and in addition are active against PDR Gram-negatives, as well as PDR Gram-positives. Their therapeutic development as inhaled dry powder antibiotics will represent a major break-through for the treatment of PDR lung infections. Notably, he was recently invited to publish a review on the SAR of teixobactins in the Annals of the New York Academy of Sciences (2020, 1459, 86-105), and has reported on the synthesis and mode of action of novel teixobactins (J Peptide Science 2019, 25 (9), e3206; mSystems 2020, 26;5(3):e00077-20).
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(2) Function and biosynthetic origin of octapeptin antibiotics
A/Prof Velkov’s second research stream focuses on the study of octapeptins, lipopeptides which possess antimicrobial activity against polymyxin-resistant extensively drug resistant (XDR) Gram-negative bacteria. His team published the first report on the total synthesis of novel octapeptins with superior activity and reduced toxicity, compared to the polymyxins. In this seminal report, the octapeptin biosynthetic cluster, mode of action and NMR solution structures were reported for the first time. The developed structure-activity and structure-toxicity models were then used to design novel octapeptins that were active against XDR bacteria. Overall, this study lays the foundations for the development of octapeptins as a new generation of novel lipopeptide antibiotics for the treatment of XDR bacterial infections. Notably, he published the first comprehensive review on the structure-activity relationships and chemistry of octapeptins in Natural Product Reports (IF 11.4). Importantly, the review covers all known octapeptin structures and as such serves as a valuable reference for peptide chemists and researchers in the field. The review was selected by the editor as the cover story for Nat Prod Rep. 2017 (34), 295-309; Cell Chem Biol 2018 (25); ACS Infect Dis 3 2018 (8), 606-619.
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(3) Pharmacology and neurotoxicity of Central Nervous System polymyxins
Over the last five years, A/Prof Velkov has made significant contributions to optimising polymyxin use by investigating the pharmacokinetics and neurotoxicity of colistin and polymyxin B using a multi-disciplinary approach (i.e. medicinal chemistry microbiology, pharmaceutical sciences, biochemistry, physico-chemistry and pharmacology). Overall, A/Prof Velkov’s polymyxin pharmacology and neurotoxicology research is at the leading edge globally. He was awarded a large 5-year NIH R01 (AI146241, 2020-2024) to study the neurotoxicity and pharmacokinetics of polymyxins in the CNS. Notable examples of A/Prof Velkov’s polymyxin pharmacology publications include: Mol Neurobiol 2016, 53, (7), 4685-700; Antimicrob Agents Chemother 2015, 59, (4), 2136-43; Pharmacol Ther 2017 (17) 30192-4; J Nat Prod 2017, 80, (1), 225-229; J Antimicrob Chemother 2017, 72, (9), 2562-2569; J Antimicrob Chemother 2017, 72, (6), 1635-1645; Antimicrob Agents Chemother 2017, 61, (6); ACS Chem Neurosci 2018 (9), 824-837; ACS Infect Dis 2020, 6 (4), 715-724.)
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(4) Systems pharmacology of novel Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) modulator/corrector drugs
A/Prof Velkov’s final research tier focuses on understanding the pharmacology and chemistry of novel Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) modulator/corrector drugs (e.g. ivacaftor/ lumcaftor/tezacaftor). His team were the first to publish on the pharmacology and off-target effects (e.g. antibacterial activity); and importantly developed the first plasma assay for measurement of drug concentrations in patient samples. His team is conducting systems-level studies of the mode-of-action and off-target effects of these drugs in collaboration with researchers at McGill University (Prof Geregley Lukacs) and Vertex Pharmaceuticals. J Molecular Recognition 2015, 28 (6), 339-348; J Chrom B 2016,1038, 57-62; J Cystic Fibrosis 2016, 15, S1-S2; ACS Infect Dis 2016, 2, (7), 478-88; JoVE, 2017, e56084; J Cystic Fibrosis 2017, 16, S24; Clinical Pharmacology & Therapeutics 2017, 101 (1), 130-141; ERJ Open Research 2018,4 (1), 00127-2017; J Cystic Fibrosis 2019, 18, S55.
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Techniques/expertise
- Antibiotic drug discovery
- Development of novel antibiotic hydrogels and dry powders
- Antimicrobial biochemical pharmacology
- Medicinal chemistry
- Nuclear Magnetic Resonance
- Isothermal Titration Calorimetry, Differential Scanning Calorimetry, thermal stability shift assays, Surface Plasmon Resonance
- Molecular modelling, de novo drug design, QSAR
- Peptide synthesis and structure-activity relationships
- Bioanalysis using LC/MS
- Imaging probes
- Epitope mapping
- Antimicrobial systems pharmacology (including genomics, transcriptomics, proteomics, metabolomics and bioinformatic analysis)
- In vitro microbiological evaluations (minimum inhibitory concentrations, anti-biofilm measurement, time-kill kinetics, antibiotic synergy)
- Mouse and rat CNS infection models
Collaborations
We collaborate with many scientists and research organisations around the world. Click on the map to see the details for each of these collaborators (dive into specific publications and outputs by clicking on the dots).
Pharmacology of CNS polymyxins
Professor Jian Li, Monash BDI, Monash University
Associate Professor Gauri Rao, University of North Carolina at Chapel Hill, USA
Development of antibiotic hydrogels for the treatment of multi-drug resistant wound infections
Professor Jian Li, Monash BDI, Monash University
Associate Professor Gauri Rao, University of North Carolina at Chapel Hill, USA
Professor David Haddelton, University of Warwick
Associate Professor Michael Whittaker, MIPS, Monash University
Mechanisms of antibacterial activity, resistance and toxicity of polymyxins
Professor Jian Li, Monash BDI, Monash University
Associate Professor Gauri Rao, University of North Carolina at Chapel Hill, USA
Dr Jing Fu, Department of Mechanical Engineering, Monash University
Associate Professor Mark Baker, University of Newcastle
Development of novel, safer polymyxinsantibiotics
Professor Jian Li, Monash BDI, Monash University
Professor Philip Thompson, MIPS, Monash University
Qpex Biopharma, San Diego, USA
Novel antibacterial polymers
Associate Professor Michael Whittaker, MIPS, Monash University
Associate Professor Cornealia Landsorfer MIPS, Monash University
Biosynthesis, chemistry and toxicity of octapeptin lipopeptide antibiotics
Professor Jian Li, Monash BDI, Monash University
Professor Philip Thompson, MIPS, Monash University
Professor Matthew Cooper, University of Queensland
Professor Mark Blastovich, University of Queensland
Studies of influenza hemagglutinin
Dr Steven Rockman CSL Pty. Ltd
Development of therapeutics targeting emerging viruses, Coronavirus, Hendra and Ebola Associate Professor Glenn Marsh, (CSIRO, AAHL, Geelong).
Development of therapeutics targeting male infertility
Associate Professor Mark Baker, University of Newcastle
Student research projects
The Velkov Lab offers a variety of Honours, Masters and PhD projects for students interested in joining our group. There are also a number of short-term research opportunities available. You are encouraged to contact Associate Professor Velkov regarding potential projects that align with the presented research themes.
Please visit Supervisor Connect to explore the projects currently available in our Lab.
