Melissa Sykes
Name: Melissa Sykes
Position: Research Fellow
Research Area: Kinetoplastid Drug Discovery
Qualifications: BSc (Hons), PhD
Biography: Melissa completed an Honours degree at Murdoch University, Western Australia on the enzyme production on virulent and avirulent strains of the plant root pathogen, Phytophthora cinnamomi. Melissa went on to work as a research assistant at Natural Product Discovery at Griffith University in 2001 and optimized assays for application in high throughput screening (HTS) campaigns over various disease areas, including biochemical and cell based assays. She worked as a research assistant at the Eskitis Institute in 2006, developing the first published 384 well HTS assay for Trypanosoma brucei brucei whole cells. Melissa has completed a PhD in the Discovery Biology department, during which she has developed a high throughput imaging based assay for the detection of compound activity against Trypanosoma cruzi amastigotes in 3T3 host cells. Melissa was awarded a Griffith University Postdoctoral Fellowship (GUPF) in 2018-2019, utlising image-based technology to assess the activity of compounds and identify the influence of differing parasite strains on compound activity. Melissa has most recently published a method to identify replicating T. cruzi parasites utilising the nuclear analogue,5-ethynyl-2′-deoxyuridine (EdU), in collaboration with Professor Sally-Ann Poulsen and Dr David Hilko, from the Griffith Institute for Drug Discovery. She has used this methodology to determine the influence of T. cruzi replication on compound activity. Melissa is currently undertaking a Griffith University New Researcher Grant (NRG) to develop 2D and microfluidic models of the gut, a reservoir which supports T. cruzi persistence in the Chronic phase of the disease.
Discovery Biology
Publications:
Ang CW, Tan L, Sykes ML, AbuGharbiyeh N, Debnath A, Reid JC, West NP, Avery VM, Cooper MA and Blaskovich MAT. Antitubercular and Antiparasitic 2-Nitroimidazopyrazinones with Improved Potency and Solubility. Journal of Medicinal Chemistry. 2020 Dec 24; 63(24): 15726-15751.
Brown RW, Abdel-Megeed AM, Keller PA, Jones AJ, Sykes ML, Kaiser M, Baell JB, Avery VM and Hyland CJT. Investigation of thiazolyl–benzothiophenamides as potential agents for African sleeping sickness. RSC Medicinal Chemistry. 2020 Sept 23; 11: 1413-1422.
Thompson AM, O’Connor PD, Marshall AJ, Francisco AF, Kelly JM, Riley J, Read KD, Perez CJ, Cornwall S, Thompson RCA, Keenan M, White KL, Charman SA, Zulfiqar B, Sykes ML, Avery VM, Chatelain E and Denny WA. Re-evaluating pretomanid analogues for Chagas disease: hit-to-lead studies reveal both in vitro and in vivo trypanocidal efficacy. European Journal of Medicinal Chemistry. 2020 Sep 18; 207: 112849.
McNamara N, Rahmani R, Sykes ML, Avery VM and Baell JB. Hit-to-lead Optimization of Novel Benzimidazole Phenylacetamides as Broad Spectrum Trypanosomacides. RCS Medicinal Chemistry. 2020 May 29; 11(6): 685-695.
Sykes ML, Hilko DH, Kung LI, Poulsen SA and Avery VM. Investigation of pyrimidine nucleoside analogues as chemical probes to assess compound effects on the proliferation of Trypanosoma cruzi intracellular parasites. PLOS Neglected Tropical Diseases. 2020 Mar 12; 14(3): e0008068.
Varghese S, Rahmani R, Russell S, Deora G, Ferrins L, Toynton A, Jones A, Sykes M, Kessler A, Eufrásio A, Cordeiro A, Sherman J, Rodriguez A, Avery VM, Piggott MJ and Baell JB. Discovery of Potent N-Ethylurea Pyrazole Derivatives as Dual Inhibitors of Trypanosoma brucei and Trypanosoma cruzi. ACS Medicinal Chemistry Letters. 2019 Sep 9; 11(3): 278-285.
Pullella GA, Wdowiak AP, Sykes ML, Lucantoni L, Sukhoverkov KV, Zulfiqar B, Sobolev AN, West NP, Mylne JS, Avery VM, Piggott MJ. Total Synthesis of the Antimalarial Ascidian Natural Product Albopunctatone. Organic Letters. Jul 19; 21(14): 5519-5523.
Houston SD, Fahrenhorst-Jones T, Xing H, Chalmers BA, Sykes ML, Stok JE, Farfan Soto C, Burns JM, Bernhardt PV, De Voss JJ, Boyle GM, Smith MT, Tsanaktsidis J, Savage GP, Avery VM and Williams CM. The cubane paradigm in bioactive molecule discovery: further scope, limitations and the cyclooctatetraene complement. Organic & Biomolecular Chemistry. 2019 Jul 17; 14(14): 1329-1335.
Jarrad AM, Ang CW, Debnath A, Hahn HJ, Woods K, Tan L, Sykes ML, Jones AJ, Pelingon R, Butler MS, Avery VM, West NP, Karoli T, Blaskovich MAT and Cooper MA. Design, synthesis and biological evaluation of 2-nitroimidazopyrazin-one/-es with antitubercular and antiparasitic activity. Journal of Medicinal Chemistry. 2018 Dec 27; 24(60): 10078-10090.
Sykes ML and Avery VM. 3-pyridyl inhibitors with novel activity against Trypanosoma cruzi reveal in vitro profiles can aid prediction of putative cytochrome P450 inhibition. Nature Scientific Reports. 2018 Mar 20; 8(1): 4901.
Duffy S, Sykes ML, Jones AJ, Shelper TB, Simpson M, Lang R, Poulsen SA, Sleebs BE, and Avery VM. Screening the MMV Pathogen Box across multiple pathogens reclassifies starting points for open source drug discovery. Antimicrobial Agents and Chemotherapy. 2017 Aug 24; 61(9): e00379-17.
Fletcher S, Lucantoni L, Sykes ML, Jones AJ, Holleran JP, Saliba KJ and Avery VM. Biological characterization of chemically diverse compounds targeting the Plasmodium falciparum coenzyme A synthesis pathway. Parasites & Vectors. 2016 Nov 17; 9(1): 589.
Sykes ML and Avery VM. Development and application of a sensitive, phenotypic, high-throughput image-based assay to identify compound activity against Trypanosma cruzi amastigotes. International Journal for Parasitology: Drugs and Drug Resistance. 2015 Dec 1; 5(3): 215-228.
Rahmani R, Ban K, Jones AJ, Ferrins L, Ganame D, Sykes ML, Avery VM, White KL, Ryan E, Kaiser M, Charman SA and Baell JB. 6-Arylpyrazine-2-carboxamides: A New Core for Trypanosoma brucei Inhibitors. Journal of Medicinal Chemistry. 2015 Sept 10; 58(17): 6753-6765.
Manos-Turvey A, Watson EE, Sykes ML, Jones AJ, Baell JB, Kaiser M, Avery VM and Payne RJ. Synthesis and Evaluation of Phenoxymethylbenzamide Analogues as Anti-Trypanosomal Agents. MedChemComm. 2015; 6(3): 403-406.
Davis RA, Beattie KD, Xu M, Yang X, Yin S, Holla H, Healy PC, Sykes M, Shelper T, Avery VM, Elofsson M, Sundin C and Quinn RJ. Solving the Supply of Resveratrol Tetramers from Papua New Guinean Rainforest Anisoptera Species That Inhibit Bacterial Type III Secretion Systems. J Nat Prod. 2014 Dec 26; 77(12): 2633-2640.
Ferrins L, Gazdik M, Rahmani R, Varghese S, Sykes ML, Jones A, Avery VM, White KL, Ryan E, Charman SA, Kaiser M, Bergstrom CA and Baell JB. Pyridyl benzamides as a novel class of potent inhibitors for the kinetoplastid Trypanosoma brucei. J Med Chem. 2014 Aug 14; 57(15): 6393-6402.
Sykes ML and Avery VM. Approaches to Protozoan Drug Discovery: Phenotypic Screening. J Med Chem. [invited review] 2013 Aug 8; 56(20): 7727-7740.
Jones AJ, Grkovic T, Sykes ML and Avery VM. Trypanocidal Activity of Marine Natural Products. Marine Drugs. [invited review] 2013 Oct 22; 11(10): 4058-4082.
Sykes ML, Baell JB, Kaiser M, Chatelain E, Ganame D, Ioset JR and Avery VM. Identification of Compounds with Anti-Proliferative Activity against Trypanosoma brucei brucei BS427 by a Whole Cell Viability Based HTS Campaign. PLoS Negl Trop Dis. 2012 Nov; 6(11): e1896.
Feng Y, Davis RA, Sykes ML, Avery VM, Quinn RJ. Iotrochamides A and B, antitrypanosomal compounds from the Australian marine sponge Iotrochota sp. Bioorg Med Chem Lett. 2012 July 15; 22(14): 4873-4876.
Xu M, Davis RA, Feng Y, Sykes ML, Shelper T, Avery VM, Camp D, and Quinn RJ. Ianthelliformisamines A-C, antibacterial bromotyrosine-derived metabolites from the marine sponge Suberea ianthelliformis. J Nat Prod. 2012 May 25; 75(50): 1001-1005.
Martin F, Grkovic T, Sykes ML, Shelper T, Avery VM, Camp D, Quinn RJ and Davis RA. Alkaloids from the Chinese Vine Gnetum montanum. J Nat Prod. 2011 Nov 28; 74(11): 2425-2430.
RA Davis, ML Sykes, VM Avery, D Camp and R J Quinn. Convolutamines I and J, anti-trypanosomal alkaloids from the bryozoan Amathia tortusa. Bioorganic & Medicinal Chemistry. 2011 Nov 15; 19(22): 6615-9.
S Yin, RA Davis, ML Sykes, T Shelper, VM Avery, M Elofsson, C Sundin , RJ Quinn. Pseudoceramines A-D, antibacterial bromotyrosine alkaloids from the marine sponge Pseudoceratina sp. Organic & Biomolecular Chemistry. 2011 Sep 9; 9(19): 6755-60.
Feng, Y.; Davis, R.A.; Sykes, M.L.; Avery, V.M.; Camp, D.; Quinn, R.J., Pseudoceratinazole A: a novel bromotyrosine alkaloid from the Australian sponge Pseudoceratina sp. Tetrahedron Letters. 51 (2010) 4847–4850
Yin, S.; Sykes, M.L.; Davis, R.A.; Shelper, T.; Avery, V.M.; Camp, D.; Quinn,R.J., New Galloylated Flavanonols from the Australian Plant, Glochidion sumatranum . Planta Medica. 2010 Nov;76(16):1877-81.
Fernandez, L.S.; Sykes, M.L.; Andrews, K.T.; Avery, V.M., Antiparasitic activity of alkaloids from plant species of Papua New Guinea and Australia. International Journal of Antimicrobial Agents 2010 Sep; 36(3):275-9.
Davis, R.A.; Demirkiran, O.; Sykes, M.L.; Avery, V.M.; Suraweera, L.; Fechner, G.A.; Quinn, R.J., 7′, 8′-Dihydroobolactone, a trypanocidal-pyrone from the rainforest tree Cryptocarya obovata. Bioorg Med Chem Lett. Jul 15 2010. 20(14):4057-4059.
Feng, Y.; Davis, R.A.; Sykes, M.L.; Avery, V.M.; Camp, D.; Quinn, R.J., Antitrypanosomal Cyclic Polyketetide Peroxides from the Australian Marine Sponge Plakoritis sp. J. Nat. Prod. Apr 23, 2010; 73(4):716-9.
Feng, Y.; Davis, R.A.; Sykes, M.L.; Avery, V.M.; Carroll, A.R.; Camp, D.; Quinn, R.J., Antitrypanosomal pyridoacridine alkaloids from the Australian ascidian polysyncraton echinatum. Tetrahedron Letters. Mar,2010; 51:2477-2479.
Sykes, M.L.; Avery, V. M., A luciferase based viability assay for ATP detection in 384-well format for high throughput whole cell screening of Trypanosoma brucei brucei bloodstream form strain 427. Parasit Vectors. 2009, 2, (1), 54
Sykes, M.L.; Avery, V. M., Development of an Alamar Blue viability assay in 384-well format for high throughput whole cell screening of Trypanosoma brucei brucei bloodstream form strain 427. Am J Trop Med Hyg. 2009, 81, (4), 665-74.
Davis, R. A.; Fechner, G. A.; Sykes, M.; Garavelas, A.; Pass, D. M.; Carroll, A. R.; Addepalli, R.; Avery, V. M.; Hooper, J. N.; Quinn, R. J., (-)-Dibromophakellin: an alpha2B adrenoceptor agonist isolated from the Australian marine sponge, Acanthella costata. Bioorg Med Chem. 2009, 17, (6), 2497-500.
Feng, Y.; Davis, R. A.; Sykes, M.; Avery, V. M.; Camp, D.; Quinn, R. J., Antitrypanosomal cyclic polyketide peroxides from the Australian marine sponge Plakortis sp. J Nat Prod. 73, (4), 716-9.
Abstracts:
Sykes, M.L and Avery, V.M. A high-throughput, image-based assay identifies new compounds with in vitro activity against the protozoan parasite Trypanosoma cruzi. The Society for Laboratory Automation and Screening (SLAS) 2017 Conference and Exhibition, 2017. February 4-8, Washington, DC, USA.
Sykes M.L, Avery V.M, Hilko D, Poulsen S.A and Kung L. Image-based identification of Trypanosoma cruzi intracellular amastigote replication utilising salvage of nucleoside analogues into parasite DNA. June 26 –29, 2017. Australian Society for Parasitology annual conference, Leura, Sydney, Australia.
Sykes, M.L and Avery, V.M. Profiling a non-biased compound library against T. cruzi amastigotes using image-based technology reveals novel CYP51 inhibitors with distinct biological profiles. September 18-22, 2016. The International Congress for Tropical Medicine and Malaria (ICTMM), Brisbane, Australia.
Sykes, M.L and Avery, V.M. Selection of compounds for target studies utilising image- and REDOX- based technologies to determine activity and efficacy against T. cruzi life cycle stages. July 13-15, 2016. Global Challenges in Neglected Tropical Diseases. Leon, Spain.
Sykes, M.L and Avery, V.M. An image-based platform identifies compounds with novel activity against Trypanosoma cruzi. New Zealand Society for Parasitology (NZSP) and The Australian Society for Parasitology (ASP) annual conference. June 19-July 2, 2015. Auckland, New Zealand.
Sykes, M.L and Avery, V.M. An image-based, high throughput assay for profiling the activity of selective inhibitors against Trypanosoma cruzi from the MMV Malaria Box Collection. American Society for Tropical Medicine and Health 64th Annual Meeting. October 25-29, 2015. Philadelphia, PA, USA.
Sykes ML and Avery VM. In vitro mode of action studies of compounds identified with activity against Trypanosoma cruzi, utilising whole-cell image based techniques. 13th International Congress of Parasitology (ICOPA). August 10-15, 2014. Mexico City, Mexico.
Sykes ML and Avery VM. Drug discovery for Trypanosoma cruzi utilizing image- and fluorescence-based assays. 13th International Congress of Parasitology (ICOPA). August 10-15, 2014. Mexico City, Mexico.
Sykes ML and Avery VM. Ciclopirox olamine with activity against Trypanosoma cruzi: in vitro mechanism of action and combination studies. 2014 Australian Society for Parasitology Annual Meeting. June 30- July 4, 2014. Canberra, Australia.
Sykes ML and Avery VM. Profiling compound activity against the life cycle stages of Trypanosoma cruzi. 24th International Conference for the World Association for the Advancement of Veterinary Parasitology, hosted by the Australian Society for Parasitology. August 25-29, 2013. Perth, Western Australia.
Sykes ML and Avery VM. The search for new compounds to inhibit Trypanosoma cruzi life cycle stages. ASMR Postgraduate Medical Research Student Conference. May 29, 2013. Brisbane, Australia.
Sykes ML and Avery VM. A 384-well imaging assay for Trypanosoma cruzi infected and non-infected 3T3 cells: determination of compound activity. Drug Discovery for Protozoan Parasites (J1). Jan 15-20, 2012. Santa Fe, New Mexico, USA.
Sykes ML and Avery VM. Imaging of Trypanosoma cruzi infected 3T3 fibroblasts: developing a 384 well assay. Australian Society for Parasitology (ASP) Annual Conference. July 10-13, 2011. Cairns, Australia.
Sykes ML and Avery VM. Identification of Inhibitors of T.cruzi Intracellular Amastigote Replication by in vitro Imaging Assays. . American Society for Tropical Medicine and Health 61st Annual Meeting. November 11-15, 2012. Atlanta, GA, USA.
Sykes ML, Avery VM, Parisot J, Street I, Baell J, Chatelain E, Ioset J. High-throughput Screening of the WEHI Compound Library Against Human African Trypanosomiasis. XIIth International Congress of Parasitology (ICOPA), Melbourne, Australia, 2010. Abs 559.
Sykes ML and Avery VM. Development and Comparative Analysis of a 384-well Luciferase-Based Viability HTS Assay for Trypanosoma brucei brucei BS427 cells. XIIth International Congress of Parasitology (ICOPA), Melbourne, Australia, 2010. Abs 1691.
Sykes ML and Avery VM. Application of a 384 well Trypanosoma brucei brucei BS 427 whole cell viability assay to the HTS of a natural product marine fractionated library. 57th American Society of Tropical Medicine and Hygiene (ASTMH) New Orleans, USA, 2008. Abs 536.
Sykes ML and Avery VM. Development of an Alamar Blue 384 Well Whole Cell Viability Assay for HTS of T.b.brucei BS 427 Cells. 57th American Society of Tropical Medicine and Hygiene (ASTMH), New Orleans, USA, 2008. Abs 163.
Travel Awards:
2017: Tony B. Academic Travel award to attend SLAS2017 6th Annual Conference and Exhibition, Washington, DC
2017: Awarded a CASS Travel Award to attend the XXXIII Annual Meeting of the Brazilian Society of Protozoology, Brazil
2015: Australian Society for Parasitology Travel Award to attend NZSP & ASP Annual Conference, Auckland
2014: BTC-AMERICAS Invited Speaker Travel costs for ICOPA, Mexico
2014: Australian Society for Parasitology Travel Award to attend 2014 ASP Annual Conference, Canberra
2013: Australian Society for Parasitology Travel Award to attend WAAVP, Perth
2012: PerkinElmer Travel Bursary to attend ASTMH 2012, Atlanta, USA
2012: BMGF Foundation Travel Award to attend Keystone Symposia: Drug Discovery for Protozoan Parasites – Santa Fe, USA
University Awards:
2020: Awarded a Griffith University New Researcher Grant Scheme to the value of $14,983
2017: Awarded a 2-year GU Postdoctoral Fellowship
2016: Pro Vice Chancellor’s Research Excellence Award – Early Career Researcher
Conference Awards:
2013: Best student presentation at WAAVP
Other
Publications:
Buchanan, M. S.; Carroll, A. R.; Edser, A.; Sykes, M.; Fechner, G. A.; Forster, P. I.; Guymer, G. P.; Quinn, R. J., Lysianadioic acid, a carboxypeptidase B inhibitor from Lysiana subfalcata. Bioorg Med Chem Lett 2008, 18, (4), 1495-7.
El-Tarabily, K.A., Sykes, M.L., Kurtböke, I.D., Hardy, G.E., Barbosa, A.M and Dekker, R.F.H. Synergistic effects of a cellulase-producing Micromonospora carbonacea and an antibiotic-producing Streptomyces violascens on the suppression of Phytophthora cinnamomi root rot of Banksia grandis. Canadian Journal of Botany 1996, 74:618-624.
Abstracts:
Sykes ML, Pitcher DJ, Fechner G, and Quinn R. Investigating AlphaScreen™ in Natural Product HTS. COMBIO. Australian Society for Biochemistry and Molecular Biology Annual Meeting, Melbourne, Australia, 2003.
