Department: Pathology and Pathogen Biology
Liam is a Senior Lecturer in the Pathology and Infectious Diseases department at the Royal Veterinary College.
Liam completed his BSc in General Science from the University of British Columbia, Vancouver, Canada in 1987. He then spent several years in the Winemaking and Brewery industry first as an assistant winemaker, then a researcher. In 1996 he completed his Molecular Biology and Genetics PhD from the University of Guelph, Ontario, Canada; the title of which was “Studies on Ribosomal RNA processing in yeasts”.
He went on to work at the University of Copenhagen in Denmark and then the Karolinska Institute in Stockholm, Sweden where he became an associate professor in the Department of Cell and Molecular Biology before coming to the Royal Veterinary College in 2007 and being appointed to his current role. Liam is also a co-founder of Tecrea Ltd www.tecrea.co.uk, an RVC spin-out company.
Bacterial resistance to conventional antibiotics is a serious health problem. Unfortunately, only a few truly new antibiotics have been discovered during the last half century. Therefore, there is a need for new strategies. Liam's laboratory works in the general area of RNA biology and has pioneered the idea of using “antisense agents” as antibacterials. Whereas conventional antibiotics typically inhibit protein targets, antisense agents target “sense” messenger RNAs. As potential drugs, antisense agents can inhibit a wider range of target genes and act with improved species selective effects. This should enable pathogen targeting without damage to the normal flora. We are working with medicinal chemists to improve cell uptake and distribution properties.
In a related study, we observed that silencing bacterial growth essential genes at the RNA level sensitises bacteria to protein level inhibitors. This synergistic effect is being extended in the laboratory to develop sensitises whole-cell assays to detect new antibacterial compounds. For example, we are screening for new new antibacterials in extracts from plants and other natural sources, where they may be present at only low concentrations.
Finally, our laboratory has developed a novel nanoparticle-based-system for delivery of nucleic acids into cells, often called "transfection". The technology is applicabel to a wide range of cell types, with potential in vivo applications..
Kamaruzzaman, NF, Firdessa, R., Good, L. (2016) Bactericidal effects of Polyhexamethylene Biguanide against intracellular Staphylococcus aureus EMRSA-15 and USA 300, Journal of Antimicrobial Chemotherapy, Jan 28. pii: dkv474
Chukwudi CU, Good L. Interaction of the tetracyclines with double-stranded RNAs of random base sequence: new perspectives on the target and mechanism of action. J Antibiot (Tokyo). 2016 Jan 20. doi: 10.1038/ja.2015.145.
Goh, S, Loeffler, A., Lloyd, DH, Nair, SP, Good, L. (2015) Oxacillin sensitization of methicillin-resistant Staphylococcus aureus and methicillin-resistant Staphylococcus pseudintermedius by antisense peptide nucleic acids in vitro. BMC Microbiology, 15:262 .
Firdessa, R., Good, L., Amstalden, M. C., Chindera, K., Kamaruzzaman, N. F., Schultheis, M., Röger, B., Hecht, n., Oelschlaeger, t.a., Meinel, l. Lühmann, T., Moll, H. (2015). Pathogen- and Host-Directed Antileishmanial Effects Mediated by Polyhexanide (PHMB). PLoS Negl Trop Dis, 9(10), e0004041. Retrieved from http://dx.doi.org/10.1371%2Fjournal.pntd.0004041
Holloway P, Musallam I, Whiting M, Good L, Van Winden, S, Silva-Fletcher, A, Ababneh, M, Abu-Basha, E, Guitian, J. (2015) Building capacity to reduce biological threats in the Middle East. Veterinary Record 2015;177:337-338 doi:10.1136/vr.h5136
Goh, S, Hohmeier, A, Stone, TC, Offord, V, Sarabia, F, Good, L (2015) Silencing of essential genes within a highly coordinated operon in Escherichia coli, Appl Environ Microbiol. 2015 Aug 15;81(16):5650-9. doi: 10.1128/AEM.01444-15
Chukwudi CU, Good L. (2015) The role of the hok/sok locus in bacterial response to stressful growth conditions. Microb Pathog. Feb;79:70-9.
Ghafourian S, Good L, Sekawi Z, Hamat RA, Soheili S, Sadeghifard N, Neela V. The mazEF toxin-antitoxin system as a novel antibacterial target in Acinetobacter baumannii. Mem Inst Oswaldo Cruz. (2014) Jul 3;109(4):502-5
Dixit, SK, Yadav, N, Kumar, S, Good, L and Awasthi, SK (2014) Synthesis and Antibacterial Activity of Novel Fluroquinolone Analogs. Medicinal Chemistry Research, in press
Mondhe M, Chessher A, Goh S, Good L, Stach JE (2014) Species-Selective Killing of Bacteria by Antimicrobial Peptide-PNAs. PLoS One. (2014) Feb 18;9(2):e89082
Goh S, Stach J, Good L. Antisense Effects of PNAs in Bacteria. Methods Mol Biol. 2014;1050:223-36.
Uguru GC, Mondhe M, Goh S, Hesketh A, Bibb MJ, Good L, Stach JE (2013) Synthetic RNA Silencing of Actinorhodin Biosynthesis in Streptomyces coelicolor A3(2). PLoS One. Jun 27;8(6):e67509.
Goltermann L, Good L, Bentin T. (2013) Chaperonins fight aminoglycoside induced protein misfolding and promote short-term tolerance in Escherichia coli. Journal of Biological Chemistry, in press.Link to paper
Johns, I, Verheyen, K., Good, L. & Rycroft, A. (2012) Antimicrobial resistance in faecal Escherichia coli isolates from horses treated with antimicrobials: a longitudinal study in hospitalised and non-hospitalised horses, Vet. Microbiology (in press).
Boberek, JM, Goh, S, Stach J & Good L. (2012) FtsZ as an antibacterial target. CABI (in press)
Good, L., Goh, S and Stach, J. (2012) Antisense in Bacteria. Methods in Molecular Biology in press
Stach, J.E.M & Good, L. (2011) Synthetic RNA silencing in bacteria - antimicrobial discovery and resistance breaking. Front. Microbio. 2:185. doi: 10.3389/fmicb.2011.00185 Link to paper
Attar L, Scott S, Goh S & Good L. (2011) A pestivirus DNA vaccine based on a non-antibiotic resistance Escherichia coli essential gene marker. Vaccine Link to paper
Arefian E, Kiani J, Soleimani M, Shariati SA, Aghaee-Bakhtiari SH, Atashi A, Gheisari Y, Ahmadbeigi N, Banaei-Moghaddam AM, Naderi M, Namvarasl N, Good L, Faridani OR (2011) Analysis of microRNA signatures using size-coded ligation-mediated PCR.. Nucleic Acids Res. 2011 Apr 12.. Link to paper
Nakashima, N., Goh, S., Good, L. Tamura, N. (2011) Multiple-gene silencing using antisense RNAs in Escherichia coli. Methods in Molecular Biology, in press.
BOBEREK, JM, STACH J, GOOD L. (2010) Genetic evidence for inhibition of bacterial division protein FtsZ by berberine. PLoS One. 2010 Oct 29;5(10):e13745. Link to paper
BANSAL, S, TAWAR, U, SINGH. M, NIKKRAVESH, A, GOOD, L TANDON, V.( 2010) Old class but new dimethoxy analogue of benzimidazole: a bacterial topoisomerase I inhibitor. International Journal of Antimicrobial Agents 35;186-90. PubMed ID 20006473
BERGQUIST, H, NIKRAVESH, A, FERNNDEZ, RD, LARSSON, V, NGUYEN, C-H, GOOD, L, ZAIN, R. (2009) Structure-specific recognition of Friedreichs ataxia (GAA)n repeats by benzoquinoquinoxaline derivatives. ChemBiochem, 10(16):2629-37. PubMed ID 19746387
GOH, S., BOBEREK, J. M., NAKASHIMA, N., STACH, J., AND GOOD, L. (2009) Concurrent growth rate and transcript analyses reveal essential gene stringency in Escherichia coli, PLoS ONE 4, e6061. PubMed ID 19557168
GOH, S. AND GOOD. (2008) Plasmid selection in Escherichia coli using an endogenous essential gene marker. BMC Biotechnology, 11;8:61. PubMed ID 18694482
FARIDANI, OF, MCINERNEY, GM, GRADIN, K AND GOOD, L. (2008) Specific ligation to double-stranded RNA for analysis of cellular RNA::RNA interactions. Nucleic Acids Research, 36(16):e99. PubMed ID 18628292
JUNKES, C., WESSOLOWSKI, A., FARNAUD, S., EVANS, R. W., GOOD, L., BIENERT, M. & DATHE, M. (2008) The interaction of arginine- and tryptophan-rich cyclic hexapeptides with Escherichia coli membranes. J Pept Sci 14, 535-543. PubMed ID 17985396
SCHEELE, C., PETROVIC, N., FAGHIHI, M. A., LASSMANN, T., FREDRIKSSON, K., ROOYACKERS, O., WAHLESTEDT, C., GOOD, L. & TIMMONS, J. A. (2007) The human PINK1 locus is regulated in vivo by a non-coding natural antisense RNA during modulation of mitochondrial function. BMC Genomics 8, 74. PubMed ID 17362513
NIKRAVESH, A., DRYSELIUS, R., FARIDANI, O. R., GOH, S., SADEGHIZADEH, M., BEHMANESH, M., GANYU, A., KLOK, E. J., ZAIN, R. & GOOD, L. (2007) Antisense PNA accumulates in Escherichia coli and mediates a long post-antibiotic effect. Mol Ther 15, 1537-1542. PubMed ID 17534267
TIMMONS, J. A. & GOOD, L. (2006) Does everything now make (anti)sense? Biochem Soc Trans 34, 1148-1150. PubMed ID 17073772
NAKASHIMA, N., TAMURA, T. & GOOD, L. (2006) Paired termini stabilize antisense RNAs and enhance conditional gene silencing in Escherichia coli. Nucleic Acids Res 34, e138. PubMed ID 17062631
LUNDIN, K. E., GOOD, L., STROMBERG, R., GRASLUND, A. & SMITH, C. I. (2006) Biological activity and biotechnological aspects of peptide nucleic acid. Adv Genet 56, 1-51. PubMed ID 16735154
FARIDANI, O. R., NIKRAVESH, A., PANDEY, D. P., GERDES, K. & GOOD, L. (2006) Competitive inhibition of natural antisense Sok-RNA interactions activates Hok-mediated cell killing in Escherichia coli. Nucleic Acids Res 34, 5915-5922. PubMed ID 17065468
DRYSELIUS, R., NIKRAVESH, A., KULYTE, A., GOH, S. & GOOD, L. (2006) Variable coordination of cotranscribed genes in Escherichia coli following antisense repression. BMC Microbiol 6, 97. PubMed ID 17118182
PARENTEAU, J., KLINCK, R., GOOD, L., LANGEL, U., WELLINGER, R. J. & ELELA, S. A. (2005) Free uptake of cell-penetrating peptides by fission yeast. FEBS Lett 579, 4873-4878. PubMed ID 16111683
KULYTE, A., NEKHOTIAEVA, N., AWASTHI, S. K. & GOOD, L. (2005) Inhibition of Mycobacterium smegmatis gene expression and growth using antisense peptide nucleic acids. J Mol Microbiol Biotechnol 9, 101-109. PubMed ID 16319499
KULYTE, A., DRYSELIUS, R., KARLSSON, J. & GOOD, L. (2005) Gene selective suppression of nonsense termination using antisense agents. Biochim Biophys Acta 1730, 165-172. PubMed ID 16135388
DRYSELIUS, R., NEKHOTIAEVA, N. & GOOD, L. (2005) Antimicrobial synergy between mRNA- and protein-level inhibitors. J Antimicrob Chemother 56, 97-103. PubMed ID 15914490
AMIRI, H., NEKHOTIAEVA, N., SUN, J. S., NGUYEN, C. H., GRIERSON, D. S., GOOD, L. & ZAIN, R. (2005) Benzoquinoquinoxaline derivatives stabilize and cleave H-DNA and repress transcription downstream of a triplex-forming sequence. J Mol Biol 351, 776-783. PubMed ID 16045927
NEKHOTIAEVA, N., ELMQUIST, A., RAJARAO, G. K., HALLBRINK, M., LANGEL, U. & GOOD, L. (2004) Cell entry and antimicrobial properties of eukaryotic cell-penetrating peptides. FASEB J 18, 394-396. PubMed ID 14656995
NEKHOTIAEVA, N., AWASTHI, S. K., NIELSEN, P. E. & GOOD, L. (2004) Inhibition of Staphylococcus aureus gene expression and growth using antisense peptide nucleic acids. Mol Ther 10, 652-659. PubMed ID 15451449
TAWAR, U., JAIN, A. K., CHANDRA, R., SINGH, Y., DWARAKANATH, B. S., CHAUDHURY, N. K., GOOD, L. & TANDON, V. (2003) Minor groove binding DNA ligands with expanded A/T sequence length recognition, selective binding to bent DNA regions and enhanced fluorescent properties. Biochemistry 42, 13339-13346. PubMed ID 14609344
RAJARAO, G. K., NEKHOTIAEVA, N. & GOOD, L. (2003) The signal peptide NPFSD fused to ricin A chain enhances cell uptake and cytotoxicity in Candida albicans. Biochem Biophys Res Commun 301, 529-534. PubMed ID 12565894
GOOD, L. (2003) Translation repression by antisense sequences. Cell Mol Life Sci 60, 854-861. PubMed ID 12827275
GOOD, L. (2003) Diverse antisense mechanisms and applications. Cell Mol Life Sci 60, 823-824. PubMed ID 12827271
DRYSELIUS, R., NEKHOTIAEVA, N., NIELSEN, P. E. & GOOD, L. (2003) Antibiotic-free bacterial strain selection using antisense peptide nucleic acid. Biotechniques 35, 1060-1064. PubMed ID 14628680
DRYSELIUS, R., ASWASTI, S. K., RAJARAO, G. K., NIELSEN, P. E. & GOOD, L. (2003) The translation start codon region is sensitive to antisense PNA inhibition in Escherichia coli. Oligonucleotides 13, 427-433. PubMed ID 15025910
TREMBLAY, A., LAMONTAGNE, B., CATALA, M., YAM, Y., LAROSE, S., GOOD, L. & ELELA, S. A. (2002) A physical interaction between Gar1p and Rnt1pi is required for the nuclear import of H/ACA small nucleolar RNA-associated proteins. Mol Cell Biol 22, 4792-4802. PubMed ID 12052886
RAJARAO, G. K., NEKHOTIAEVA, N. & GOOD, L. (2002) Peptide-mediated delivery of green fluorescent protein into yeasts and bacteria. FEMS Microbiol Lett 215, 267-272. PubMed ID 12399045
GOOD, L. (2002) Antisense inhibition of bacterial gene expression and cell growth. Methods Mol Biol 208, 237-248. PubMed ID 12229292
ERIKSSON, M., NIELSEN, P. E. & GOOD, L. (2002) Cell permeabilization and uptake of antisense peptide-peptide nucleic acid (PNA) into Escherichia coli. J Biol Chem 277, 7144-7147. PubMed ID 11739379
GOOD, L., AWASTHI, S. K., DRYSELIUS, R., LARSSON, O. & NIELSEN, P. E. (2001) Bactericidal antisense effects of peptide-PNA conjugates. Nat Biotechnol 19, 360-364. PubMed ID 11283595
WAHLESTEDT, C., SALMI, P., GOOD, L., KELA, J., JOHNSSON, T., HOKFELT, T., BROBERGER, C., PORRECA, F., LAI, J., REN, K., OSSIPOV, M., KOSHKIN, A., JAKOBSEN, N., SKOUV, J., OERUM, H., JACOBSEN, M. H. & WENGEL, J. (2000) Potent and nontoxic antisense oligonucleotides containing locked nucleic acids. Proc Natl Acad Sci U S A 97, 5633-5638. PubMed ID 10805816
GOOD, L., SANDBERG, R., LARSSON, O., NIELSEN, P. E. & WAHLESTEDT, C. (2000) Antisense PNA effects in Escherichia coli are limited by the outer-membrane LPS layer. Microbiology 146 ( Pt 10), 2665-2670. PubMed ID 11021941
INTINE, R. V., GOOD, L. & NAZAR, R. N. (1999) Essential structural features in the Schizosaccharomyces pombe pre-rRNA 5' external transcribed spacer. J Mol Biol 286, 695-708. PubMed ID 10024444
GOOD, L. & NIELSEN, P. E. (1999) Peptide nucleic acid (PNA) antisense effects in Escherichia coli. Curr Issues Mol Biol 1, 111-116. PubMed ID 11475695
GOOD, L. & NIELSEN, P. E. (1998) Antisense inhibition of gene expression in bacteria by PNA targeted to mRNA. Nat Biotechnol 16, 355-358. PubMed ID 9555726
GOOD, L. & NIELSEN, P. E. (1998) Inhibition of translation and bacterial growth by peptide nucleic acid targeted to ribosomal RNA. Proc Natl Acad Sci U S A 95, 2073-2076. PubMed ID 9482840
GOOD, L. & NIELSEN, P. E. (1997) Progress in developing PNA as a gene-targeted drug. Antisense Nucleic Acid Drug Dev 7, 431-437. PubMed ID 9303195
GOOD, L. & NAZAR, R. N. (1997) Plasmid mini-preparations from culture streaks. Biotechniques 22, 404-406. PubMed ID 9067008
GOOD, L., INTINE, R. V. & NAZAR, R. N. (1997) The ribosomal-RNA-processing pathway in Schizosaccharomyces pombe. Eur J Biochem 247, 314-321. PubMed ID 9249042
GOOD, L. & NAZAR, R. N. (1995) Visualization of CsCl/EtdBr plasmid preparations under visible light. Biotechniques 18, 556-558. PubMed ID 7598879
ABOU ELELA, S., GOOD, L. & NAZAR, R. N. (1995) An efficiently expressed 5.8S rRNA 'tag' for in vivo studies of yeast rRNA biosynthesis and function. Biochim Biophys Acta 1262, 164-167. PubMed ID 7599193
MELEKHOVETS, Y. F., GOOD, L., ELELA, S. A. & NAZAR, R. N. (1994) Intragenic processing in yeast rRNA is dependent on the 3' external transcribed spacer. J Mol Biol 239, 170-180. PubMed ID 8196052
GOOD, L., ELELA, S. A. & NAZAR, R. N. (1994) Tetrahymena ribozyme disrupts rRNA processing in yeast. J Biol Chem 269, 22169-22172. PubMed ID 8071340
ABOU ELELA, S., GOOD, L., MELEKHOVETS, Y. F. & NAZAR, R. N. (1994) Inhibition of protein synthesis by an efficiently expressed mutation in the yeast 5.8S ribosomal RNA. Nucleic Acids Res 22, 686-693. PubMed ID 8127718
GOOD, L. & NAZAR, R. N. (1992) An improved thermal cycle for two-step PCR-based targeted mutagenesis. Nucleic Acids Res 20, 4934. PubMed ID 1408812
His interests centre around genetics and general microbiology, which he teaches to the 2nd and 3rd year BVetMed undergraduates. He also supervises graduate PhD students with theses in his field.
He has a long-term interest in developing and improving antimicrobial strategies.