Toxins and Drug Discovery

Prof P. Gopalakrishnakone is a world leader in the characterization of the structure and function of animal and plant toxins and chemical poisons, which contain highly specific and biologically active components. He has contributed significantly to the body of knowledge regarding the anatomy of snake venom glands and the development of drug candidates from animal toxins. Prof Gopal pioneered the development of the NUS Venom and Toxin Research Programme, which has put NUS at the forefront of toxin research internationally.  The technology platform that has been built over the years under the Venom and Toxin Research Programme, coupled with its extensive library of protein and peptides, has enabled Prof Gopal and his team to complete the discovery process of lead candidates in time and to transfer valuable supplementary information to the next discovery steps involving profiling and optimization of lead candidates.  The objective is to characterize the venom components and natural toxins at a molecular level and identify promising compounds amenable to the development of novel human therapeutics.  Prof Gopal’s lab has identified over twenty peptides with unique medical indications from venom-based proteins with some already under development as therapeutics.Prof Gopal’s research studies includes structure function studies (toxin detection, biosensors, antitoxins and neutralization factors), toxicogenomics and expression studies,  antimicrobial peptides from venoms and toxins and PLA2 inhibitors as potential drug candidate for inflammatory diseases.  The techniques he employs include quantum dots to toxinology, computational biology, microarrays and protein chips. He has patented analgesic peptide, anti inflammatory peptide as well as anti rheumatoid arthritis peptides. He is exploring various possibilities of delivery systems for these peptides to target sites and administration of these peptides orally, transdermally, ocular and injections.Prof Gopal has over 100 international peer-reviewed papers in venom and toxin research, drug discovery, biosensors, and toxinogenomics. His research awards include the Outstanding University Researcher Award from the National University of Singapore (1998); Ministerial Citation, NSTB Year 2000 Award in Singapore; and the Research Excellence Award from the Faculty of Medicine, National University of Singapore (2003). His awards in teaching include, Faculty Teaching Excellence Award 2003/4 & NUS Annual Teaching Excellence Award 2003/4. He also received the Faculty Teaching Excellence Award in 2009/10 and the Annual Teaching Excellence Award, NUS FOR 2009/10. He is the President of International Society on Toxinology till 2012, and is a member of the editorial board of Toxicon, the official journal of the International Society on Toxinology. Dr. Lourdes J. Cruz is Professor Emeritus of the University of the Philippines Diliman (UPD) and a national scientist. Dr. Cruz obtained her B.S. Chemistry degree from UPD in 1962 and her M.S. and Ph.D. in biochemistry from the University of Iowa in 1966 and 1968. She worked briefly at IRRI before joining the Department of Biochemistry in UP Manila in 1970 where she served as Chair of the Department of Biochemistry and Molecular Biology from 1980 to 1986, then transferred to the Marine Science Institute of UPD in 1989. From 1976 to 2006, she spent 3–6 months every year at the University of Utah collaborating with Prof. Baldomero M. Olivera on the elucidation of the biochemical and molecular nature of toxins from the venomous Conus marine snail, which are now used as pharmacological tools in the study of brain function and in drug development. Her research activities include marine toxins involved in harmful algal blooms. Dr. Cruz served for 12 years as the delegate of the Philippine Society for Biochemistry & Molecular Biology (PSBMB) to the federation, FAOBMB and for nine years as delegate to the international union, IUBMB.  Her international awards include the Sven Brohult Award of the International Foundation for Science (IFS) in 1993, ASEAN Outstanding Scientist & Technologist in 2001, the L’Oreal-UNESCO Award for Women in Science in 2010, and the Outstanding Alumnus Award of the University of Iowa’s Carver College of Medicine in 2011. Prof. Cruz is a member of the National Academy of Science and Technology PHL and a fellow of The World Academy of Sciences. As the current Chair of the Regional Committee for Asia and the Pacific of the International Council for Science (ICSU), she is very actively involved in the newly established program on the “Sustainability Initiative for the Marginal Seas of South and East Asia”. Prof. Sulan Luo, Ph.D., is Distinguished Professor of Chang Jiang Scholars Program, and the director of Key Lab for Tropical Biological Resources, Ministry of Education at Hainan University. She is the director of KeyLab for Marine Drug of Haikou at Hainan University, as well. Prof. Luo is the team leader of “Program for Changjiang Scholars and Innovative Research Team in niversity” of Ministry of Education. Her research interests focus on structure and function of conopeptides native to Hainan and their molecular receptors (ion channels), molecular biology, Xenopus oocytes electrophysiology, biotechnology and marine medicine, and neuropeptides in marine organisms, among others. She established a new center for experimental biotechnology and department of pharmacy engineering in Hainan University. Prof. Luo has been the core leader of Major International Joint Research Project of National Natural Science Foundation of China, the State High-Tech Research and Development Project (863) of the Ministry of Science and Technology of China Grant, Program for International Science & Technology Cooperation Program of China Grant, and National Natural Science Foundation of China Grant, among others. She is the author of 112 scientific publications and inventor of 11 patents. Prof. Luo discovered six new Hainan conotoxins target nicotinic acetylcholine receptors (nAChRs) subtypes, including atypical α-conotoxin LtIA targets a novel microsite of the a3b2 nAChR, α-conotoxin TxIB that selectively targets a6/a3b2b3 nAChR,  α4/7-conotoxin LvIA selectively blocks α3β2 vs. α6/α3β2β3, α-conotoxin TxID that potently blocks rat α3β4 nAChR, a novel inhibitor of a9a10 nAChR delineates a new conotoxin superfamily etc. The nAChRs are potential targets for the treatment of various neuropsychiatric diseases, including addiction, pain and Parkinson’s disease etc. These Hainan conotoxins show great potential in medical applications.

Crotoxin from Crotalus durissus terrificus and Crotoxin-Related Proteins: Structure and Function Relationship.- Dexamethasone Antagonizes Myotoxic and Inflammatory Effects Induced by Bothrops Snake Venoms.- Inflammatory Action of Secretory PLA2 from Snake Venoms.- Natural Inhibitors of Snake Venom Metallopeptidases.- Production and Utilization of Snake Antivenoms in South America.- Snake Venom Components as Basis for Biologically Active Synthetic Peptides.- Antiproliferative Effects of Snake Venom Phospholipases A2 and Their Perspectives for Cancer Treatment.- Conotoxins and Drug Discovery with Special Reference to Hainan Species.- Conotoxins as Tools in Research on Nicotinic Receptors.- Random Peptide Library for Ligand and Drug Discovery.- Synthetic Peptides and Drug Discovery.- Bee Venom and Pain.- L-Amino Acid Oxidase from Venoms.- Myotoxin Inhibitors.- Computational Approaches for Animal Toxins to Aid DrugDiscovery.- Toad Poison and Drug Discovery.- Venoms as Sources of Novel Anti-parasitic Agents.- Intriguing Cystine-Knot Miniproteins in Drug Design and Therapeutics.- Intriguing Cystine-Knot Miniproteins in Drug Design and Therapeutics.