Staff Profile

Introduction

Principal research interests include the ecology of marine actinomycetes, (diversity, abundance and biogeography), novel natural products from marine actinomycetes, the application of peptide nucleic acids in species-specific bactericide and the development of antisense-based antibacterial screens

Background

Abyssomicin made the National press including The Sun, and The Guardian

Qualifications

• BSc 1996 Microbiology and Biotechnology (University of Kent)
• PhD 2001 Microbiology (University of Kent)

Memberships

• Member of the Society of General Microbiology
• Member of the American Society for Microbiology

Google Scholar Profile

Current Work

Verrucosispora AB18-032 and natural products


One of our main research interests is the marine actinomycete species Verrucosispora AB18-032. This species is responsible for the production of the first-in-class natural product abyssomicin C. Abyssomicin C inhibits the essential folic acid pathway present in bacteria and plants. In collaboration with Prof Sussmuth, we recently published how abyssomicin C is biosynthesized. We have completed the full genome sequence of the abyssomicin producer and are currently using genome mining techniques to identify novel bioactive compounds.

Peptide-PNA conjugates as species-specific antimicrobials


This research is funded by a Nuffield new lecturers award. The aim of the research is to develop peptide-PNA conjugates that can specifically target, and prevent transcription of, specific essential bacterial genes. Research in other labs has shown that it is possible to use such conjugates to target bacterial genes. However, the novelty of this research lies in the combination of using essential genes with species-specific sequences. Thus, peptide-PNA conjugates could be used to select target species without providing selection pressure for resistance in non-target organisms. We have recently proven that it is indeed possible to target species for bactericide in a species-specific manner that is not achievable using conventional antibiotics (see publications).

Antisense-based antimicrobial screens


This research is funded by a BBSRC DTG grant. The aim of the study is to develop and validate screens for antibacterial compounds. Induction of antisense RNA reduces the expression of its cognate protein and sensitises the strain to inhibition of that protein. This is of particular value in natural products research where effective antimicrobial compounds may be present in extracts but in amounts below the minimum inhibitory concentration for a wild-type screen. We have recently used this methodology to identify plant-derived inhibitors of the bacterial cell division protein FtsZ . We have also used this methodology to identify the stringency of requirement for essential genes in E. coli that will aid in prioritising targets for drug discovery. Current research aims at validating the screens by correlating protein abundance with mRNA abundance during antisense expressing and using microarrays to demonstrate the specificity of the gene silencing. As such we are developing and validating novel methods that will enable absolute quantification of the amount of specific protein per cell in E. coli.

Research Roles

School of Biology research committee member.

Postgraduate Supervision

Esteem Indicators

Act as a referee for a number of microbiology journals.
Referee for BBSRC, NERC and the NSF (USA)


Invited to write review article for Trends in Microbiology


Invited to give research papers at International conferences (ISBA, ISME)


Invited to contributed chapters to multi-authored books including American Society for Microbiology Press: Microbial Diversity and Bioprospecting


Was invited to be one of five academics on the Department of Trade and Industry’s Global Watch Mission to Japan on Bioprocessing.

Funding

Nuffield Foundation new lecturers award: Species-specific peptide nucleic acid (PNA)-based antibiotics

BBSRC: Identification, cloning and heterologous expression of the abyssomicin C biosynthetic gene cluster

BBSRC Partnering China award: Cryptic biosynthetic gene clusters from marine bacteria

Royal Society: Genome mining of Verrucosispora AB18-032 

Industrial Relevance

Founding director (along with Prof Barnes, Dr Singleton and Dr Taybi) of Geneius Laboratories, a spin-out company which is revolutionizing microbial testing and food analysis using state-of-the-art DNA technology. Geneius has recently won the CELS most promising start-up award.

Academic partner on 4 Collaborative Innovation Partnership (CIP) awards

Undergraduate Teaching

BIO1010 Biology in Action

BIO2017 Microbiology 2

BIO3019 Genomics

BIO3021 Laboratory Workshop

BIO3030 Antimicrobial Drug Discovery

BIO3194 Biological Literature Review 

BIO3095 Biological Information Project

BIO3096 Research Project

Postgraduate Teaching

BIO8041 Antimicrobial Drug Discovery

BIO8043 Techniques in Molecular Biology

BIO8047 Entrepreneurship in Biotechnology

BIO8046 Applied Bioinformatics

BIO8096 Research Thesis

• Lees NR, Han LC, Byrne MJ, Davies JA, Parnell AE, Moreland PEJ, Stach JEM, van der Kamp MW, Willis CL, Race PR. An Esterase‐like Lyase Catalyzes Acetate Elimination in Spirotetronate/Spirotetramate Biosynthesis. Angewandte Chemie International Edition 2019, 58(8), 2305-2309.
• Maschio L, Parnell AE, Lees NR, Willis CL, Schaffitzel C, Stach JEM, Race PR. Cloning, expression, and purification of intact polyketide synthase modules. In: Methods in Enzymology. Academic Press, 2019, pp.63-82.
• Villapún VM, Zhang H, Howden C, Cheung Chow L, Esat F, Pérez P, Sort J, Bull S, Stach J, González S. Antimicrobial and wear performance of Cu-Zr-Al metallic glass composites. Materials and Design 2017, 115, 93-102.
• Chindera K, Mahalo M, Sharma A, Horsley H, Kloc-Muniak K, Kamaruzzamabn N, Kumar S, McFarlane A, Stach J, Bentin T, Good L. The antimicrobial polymer PHMB enters cells and selectively condenses bacterial chromosomes. Nature Scientific Reports 2016, 6, 23121.
• Byrne MJ, Lees NR, Han LC, van der Kamp MW, Mulholland AJ, Stach JEM, Willis CL, Race PR. The Catalytic Mechanism of a Natural Diels-Alderase Revealed in Molecular Detail. Journal of the American Chemical Society 2016, 138(19), 6095-6098.
• Goh S, Stach JEM, Good L. Antisense effects of PNAs in bacteria. Methods in Molecular Biology 2014, 1050, 223-236.
• Mondhe M, Chessher A, Goh S, Good L, Stach JEM. Species-selective killing of bacteria by antimicrobial peptide-PNAs. PLoS ONE 2014, 9(2), e89082.
• Goodfellow M, Brown R, Ahmed L, Pathom-aree W, Bull AT, Jones AL, Stach JEM, Zucchi TD, Zhang LX, Wang J. Verrucosispora fiedleri sp nov., an actinomycete isolated from a fjord sediment which synthesizes proximicins. Antonie van Leeuwenhoek 2013, 103(3), 493-502.
• Uguru GC, Mondhe M, Goh S, Hesketh A, Bibb MJ, Good L, Stach JEM. Synthetic RNA Silencing of Actinorhodin Biosynthesis in Streptomyces coelicolor A3(2). PLoS ONE 2013, 8(6), e67509.
• Prieto-Davo A, Villarreal-Gomez LJ, Forschner-Dancause S, Bull AT, Stach JEM, Smith DC, Rowley DC, Jensen PR. Targeted search for actinomycetes from nearshore and deep-sea marine sediments. FEMS Microbiology Ecology 2013, 84(3), 510-518.
• Ghosal A, Vitali A, Stach JEM, Nielsen PE. Role of SbmA in the Uptake of Peptide Nucleic Acid (PNA)-Peptide Conjugates in E. coli . ACS Chemical Biology 2012, 8(2), 360-367.
• Goodfellow M, Stach JEM, Brown R, Bonda ANV, Jones AL, Mexson J, Fiedler HP, Zucchi TD, Bull AT. Verrucosispora maris sp nov., a novel deep-sea actinomycete isolated from a marine sediment which produces abyssomicins. Antonie van Leeuwenhoek 2012, 101(1), 185-193.
• Gottardi EM, Krawczyk JM, von Suchodoletz H, Schadt S, Mühlenweg A, Uguru GC, Pelzer S, Fiedler H-P, Bibb MJ, Stach JEM, Süssmuth RD. Abyssomicin Biosynthesis: Formation of an Unusual Polyketide, Antibiotic-Feeding Studies and Genetic Analysis. ChemBioChem 2011, 12(9), 1401-1410.
• Roh H, Uguru GC, Ko HJ, Kim S, Kim B-Y, Goodfellow M, Bull AT, Kim KH, Bibb MJ, Choi IG, Stach JEM. Genome Sequence of the Abyssomicin- and Proximicin-Producing Marine Actinomycete Verrucosispora maris AB-18-032. Journal of Bacteriology 2011, 193(13), 3391-3392.
• Good L, Stach JEM. Synthetic RNA silencing in bacteria - antimicrobial discovery and resistance breaking. FRONTIERS IN MICROBIOLOGY 2011, 2.
• Stach J. Antimicrobials: Treasures from the oceans. Microbiology Today 2010, 37(2), 104-109.
• Boberek JM, Stach JEM, Good L. Genetic Evidence for Inhibition of Bacterial Division Protein FtsZ by Berberine. PLoS One 2010, 5(10), e13745.
• Hohmann C, Schneider K, Bruntner C, Irran E, Nicholson G, Bull AT, Jones AL, Brown R, Stach JEM, Goodfellow M, Beil W, Kramer M, Imhoff JF, Sussmuth RD, Fiedler HP. Caboxamycin, a new antibiotic of the benzoxazole family produced by the deep-sea strain Streptomyces sp NTK 937. Journal of Antibiotics 2009, 62(2), 99-104.
• Goh S, Boberek J, Nakashima N, Stach J, Good L. Concurrent Growth Rate and Transcript Analyses Reveal Essential Gene Stringency in Escherichia coli. PLoS One 2009, 4(6), e6061.
• Maldonado LA, Stach JEM, Ward AC, Bull AT, Goodfellow M. Characterisation of micromonosporae from aquatic environments using molecular taxonomic methods. Antonie van Leeuwenhoek 2008, 94(2), 289-298.
• Antony-Babu S, Stach JEM, Goodfellow M. Genetic and phenotypic evidence for Streptomyces griseus ecovars isolated from a beach and dune sand system. Antonie van Leeuwenhoek, International Journal of General and Molecular Microbiology 2008, 94(1), 63-74.
• Bull AT, Stach JEM. Marine actinobacteria: new opportunities for natural product search and discovery. Trends in Microbiology 2007, 15(11), 491-499.
• Herrera A, Hery M, Stach JEM, Jaffre T, Normand P, Navarro E. Species richness and phylogenetic diversity comparisons of soil microbial communities affected by nickel-mining and revegetation efforts in New Caledonia. European Journal of Soil Biology 2007, 43(2), 130-139.
• Maldonado LA, Stach JEM, Pathom-Aree W, Ward AC, Bull AT, Goodfellow M. Diversity of cultivable actinobacteria in geographically widespread marine sediments. Antonie van Leeuwenhoek, International Journal of General and Molecular Microbiology 2005, 87(1), 11-18.
• Stach JEM, Bull AT. Estimating and comparing the diversity of marine actinobacteria. Antonie van Leeuwenhoek, International Journal of General and Molecular Microbiology 2005, 87(1), 3-9.
• Bringmann G, Lang G, Maksimenka K, Hamm A, Gulder TAM, Dieter A, Bull AT, Stach JEM, Kocher N, Muller WEG, Fiedler H-P. Gephyromycin, the first bridged angucyclinone, from Streptomyces griseus strain NTK 14. Phytochemistry 2005, 66(11), 1366-1373.
• Bull AT, Stach JEM, Ward AC, Goodfellow M. Marine actinobacteria: Perspectives, challenges, future directions. Antonie van Leeuwenhoek, International Journal of General and Molecular Microbiology 2005, 87(1), 65-79.
• Stach JEM, Maldonado LA, Ward AC, Bull AT, Goodfellow M. Williamsia maris sp. nov., a novel actinomycete isolated from the Sea of Japan. International Journal of Systematic and Evolutionary Microbiology 2004, 54(1), 191-194.
• Bull AT, Stach JEM. An overview of biodiversity - estimating the scale. In: Bull, A.T, ed. Microbial Diversity and Bioprospecting. Washington, DC, USA: ASM Press, 2003, pp.15-28.
• Stach JEM, Maldonado LA, Ward AC, Goodfellow M, Bull AT. New primers for the class Actinobacteria: Application to marine and terrestrial environments. Environmental Microbiology 2003, 5(10), 828-841.
• Stach JEM, Maldonado LA, Masson DG, Ward AC, Goodfellow M, Bull AT. Statistical Approaches for Estimating Actinobacterial Diversity in Marine Sediments. Applied and Environmental Microbiology 2003, 69(10), 6189-6200.
• Stach JEM, Burns RG. Enrichment versus biofilm culture: a functional and phylogenetic comparison of polycyclic aromatic hydrocarbon-degrading microbial communities. Environmental Microbiology 2002, 4(3), 169-182.
• Burns RG, Stach JEM. Microbial ecology of soil biofilms: substrate bioavailability, bioremediation and complexity. In: Violante, A, ed. Soil Mineral-organic Matter-microorganism Interactions and Ecosystem Health. Amsterdam: Elsevier Press, 2002, pp.17-42.
• Stach JEM, Bathe S, Clapp JP, Burns RG. PCR-SSCP comparison of 16S rDNA sequence diversity in soil DNA obtained using different isolation and purification methods. FEMS Microbiology Ecology 2001, 36(2-3), 139–151.