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Research Interests

Biomimetics on enhanced calcification and related phenomena: Light-enhanced calcification in the giant clam, Tridacna squamosa, in association with symbiotic zooxanthellae

Biomimicry is the science of looking directly to nature’s best ideas and general “know-how”, and then emulating or drawing inspiration from them to solve human problems. After 3.8 billion years of nature’s research and development in the biological world, failures are fossils, and what surrounds us is the secret to survival. The core idea of biomimicry is that nature, imaginative by necessity, has already solved many of the problems humans are grappling with. Animals, plants, and microbes are the consummate engineers. They have found what works, what is appropriate, and most importantly, what lasts here on Earth. The giant clam, Tridacna squamosa harbours symbiotic zooxanthellae and can employ light enhanced calcification to grow to gigantic size within a relatively short period of time (as compared with ordinary clams). I am interested to perform a biomimetic study on light-enhanced calcification in the giant clam, T. squamosa, with the aims to derive means to enhance bone growth and repair in patients with fractured bone and to effectively defend against oxidative stress, with the help of novel bioactive anti-oxidants, during aging and in certain diseases?

Biomimetics on electrocommunication and electrolocation: Navigation and location using marine animal models

Existing communication tools in the marine domain rely mainly on acoustic and electromagnetic means for communication, navigation and sensing. However, these methods are limited as they are detectable because they involve wave propagation. Electrostatic and magneto-static means may offer a better solution as there is no wave propagation. Advantages include a much smaller loss of energy and less disruption to the ambient environment. Wave dispersion effects which lead to interference (and detection) can also be avoided. Electric fishes are able to ‘see’ objects in an environment where vision is useless (at night, or in murky water) using a process called active electrolocation. By a combination of electrogeneric and electroreceptive capabilities, these fishes are able to communicate one another using electric signals. Other fishes such as sharks, rays and skates are use passive electroreception to locate prey animals buried in sand by detecting the weak electric field given off by the prey. I am interested in using molecular and transcirptomic techniques to study the electric organ and ampullary electroreceptors of marine (torpedo ray) and freshwater (electric eel) electric fishes.

Bimimetics on suspended animation: Metabolic rate reduction in aestivating African lungfishes and swamp eel.

Lungfishes (or dipnoans as they are “dual breathers”) are an archaic group of fishes, characterized by the possession of a lung opening off the ventral side of the oesophagus. The African lungfishes (Protopterus aethiopicus, Protopterus annectens, Protopterus amphibious and Protopterus dolloi) can aestivate in subterranean mud cocoons for long periods of time (up to 5 years). On the other hand, the swamp eel can aestivate in mud without forming a cocoon for months during drought. I am interested in (a) how dehydration is avoided, (b) how metabolic rate is reduced to prevent exhaustion of internal reserves, and (c) how the pollution of the internal environment is ameliorated. Answers to all these questions have important biomedical implications.

Biomimetics on how to deal with ammonia toxicity (e.g. in the case of liver failure)

A. Strategies adopted by air-breathing fishes to defend against ammonia toxicity during aerial exposure.

Fishes currently being studied include the mudskippers (Periophthalmodon schlosseri, Boleophthalmus boddaerti, and Periophthalmus chrysospilos), the marble goby (Oxyeleotris marmoratus), the four-eyed sleeper (Bostrichythes sinensis), the snakeheads (Channa asiatica and Channa micropeltes), the Oriental weather loach (Misgurnus anguillicaudatus), the African sharptooth catfish (Clarias gariepinus) and the swamp eel (Monopterus albus). Liver failure in mammals leads to hepatic encephalopathy manifested as comma followed by death. It is hoped that results obtained will reveal adaptations involved in conferring these air-breathing fishes high ammonia-tolerance, which can be of value for the formulation of treatments for patients with liver failure. At present, efforts are focused on (1) the role of glutamine synthetase in ammonia detoxification and how it can be up-regulated in response to an ammonia surge, and (2) active transport of NH4+ and H+ excretion via V-type H+-ATPase. B. Urea synthes

B. Urea synthesis and the ornithine-urea cycle.

Animals currently being studied include the giant African snail (Achatina fulica), the Asian freshwater stingray (Himantura signifer), the South American stingray (Potamotrygon motoro), the marine blue-spotted stingray (Taeniura lymma), the African lungfishes (Protopterus dolloi, Protopterus aethiopicus and Protopterus annectens), the Chinese fire-belly newt (Cynops orientalis), the crab-eating frog (Rana cancrivora), and the soft-shelled turtle (Amyda cartilaginea). Mammals detoxify ammonia to urea. However, whether the usurpation of the arginine synthetic pathway for urea production was directed to ammonia detoxification or osmotic retention of water is a moot point. Attempts are made in my laboratory to elucidate the role of urea synthesis in various animals during emersion, exposure to environmental ammonia, injection/infusion with ammonia or feeding. We aim to elucidate how the ornithine-urea cycle capacity of these animals can be up-regulated under certain environmental conditions.

C. Ammonia toxicity to brains of vertebrates.

Fish currently being studied are those which had extraordinary capacity to synthesize and accumulate glutamine and/or to tolerate high levels of ammonia in their brains. These include the mudskippers, the swamp eel and the African catfish. Specifically we focus on (1) the deleterious effects of glutamine synthesis and accumulation and (2) glutamate dysfunction leading to activation of the N-methyl-D-aspartate (NMDA) type glutamate receptor, using pharmacological agents like MK-801 and MSO. I am interested in finding out why, unlike mammals, some of these unique fishes have very high tolerance of ammonia in their brains, and how ammonia toxicity to mammalian brains can be ameliorated.

Research Publications (2013-Present)

1. Ip, Y. K., Soh, M. M. L., Chen, X. LO., Ong, J. L. Y., Chng, Y. R., Ching B., Wong, W. P., Lam, S. H. and Chew, S. F. (2013). Molecular characterization of branchial aquaporin 1aa and effects of seawater acclimation, emersion or ammonia exposure on its mRNA expression in the gills, gut, kidney and skin of the freshwater climbing perch, Anabas testudineus. PLoS One 8(4) e61163 DOI: 10.1371/journal.pone.0061163

2. Ip, Y. K., Lee, S. M. L., Wong, W. P., Chew, S. F. (2013). The Chinese soft-shelled turtle, Pelodiscus sinensis, decreases nitrogenous excretion, reduces urea synthesis and suppresses ammonia production during emersion. J. Exp. Biol. 216, 1650-1657.

3. Wong, S. Z. H., Ching, B., Chng, Y. R., Wong, W. P., Chew, S. F. and Ip, Y. K. (2013).Ascorbic Acid Biosynthesis and Brackish Water Acclimation in the Euryhaline Freshwater White-Rimmed Stingray, Himantura signifier. PLoS ONE 8(6): e66691. doi:10.1371/journal.pone.0066691

4. Ching, B., Chen, X. L.,Yong, J. H. A., Wilson, J. M., Hiong, K. C., Sim, E. W. L., Wong, W. P., Lam, S. H., Chew, S. F. and Ip, Y. K. (2013). Increases in apoptosis, caspase activity and expression of p53 and bax, and the transition between two types of mitochondrion-rich cells, in the gills of the climbing perch, Anabas testudineus, during a progressive acclimation from freshwater to seawater. Front. Physiol. 4:135. doi: 10.3389/fphys.2013.00135

5. Amelio, D., Garofalo, F., Wong, W. P., Chew, S. F., Ip, Y. K., Cerra, M. C. and Tota B. (2013). Nitric oxide synthase-dependent “On/Off” switch and apoptosis in freshwater and aestivating lungfish, Protopterus annectens: skeletal muscle versus cardiac muscle. Nitric Oxide 32, 1-12.

6. Hiong, K. C., Ip, Y. K., Wong, W. P. and Chew, S. F. (2013). Differential gene expression in the brain of the African lungfish, Protopterus annectens, after six days or six months of aestivation in air. PLoS ONE 8(8): e71205. doi:10.1371/journal.pone.0071205.

7. Ip, Y. K., Hou, Z., Chen, X. L., Ong. J. L. Y., Chng, Y. R., Ching, B., Hiong, K. C. and Chew, S. F. (2013). High brain ammonia tolerance and down-regulation of Na+:K+:2Cl- cotransporter 1b mRNA and protein expression in the brain of the swamp eel, Monopterus albus, exposed to environmental ammonia or terrestrial conditions. PLoS ONE 8(9): e69512. doi:10.1371/journal.pone.0069512.

8. Ip, Y. K., Hiong, K. C., Wong, S. Z. H., Ching, B., Chen, X. L., Soh, M. M. L., Chng, Y. R., Ong, J. L. Y., Wilson, J. M. and Chew, S. F. (2013). Branchial Na+:K+:2Cl− cotransporter 1 and Na+/K+-ATPase α-subunit in a brackish water-type ionocyte of the euryhaline freshwater white-rimmed stingray, Himantura signifer. Front. Physiol. 4:362. doi: 10.3389/fphys.2013.00362.

9. Chen, X. L., Wee, N. L. J. E., Hiong, K. C., Ong, J. L. Y., Chng, Y. R., Ching, B., Wong, W. P., Chew, S. F. and Ip, Y. K. (2013). Properties and expression of Na+/K+-ATPase α-subunit isoforms in the brain of the swamp eel, Monopterus albus, which has unusually high brain ammonia tolerance. PLoS ONE 8(12): e84298. doi:10.1371/journal.pone.0084298.

10. Icardo, J. M, Wong, W. P., Colvee, E., Loong, A. M., Zapata A. G and Ip, Y. K. (2014). Lympho-granulocytic tissue associated with the wall of the spiral valve in the African lungfish Protopterus annectens. Cell Tissue Res 355: 397-401.

11. Chew, S. F., and Ip, Y. K. (2014). Excretory nitrogen metabolism and defense against ammonia toxicity in air-breathing fishes. J. Fish Biol. 84: 603-638 (doi: 10.1111/jfb.12279).

12. Li, Z., Lui, E. Y., Wilson, J. M., Ip, Y. K., Lin, Q., Lam, T. J. and Lam, S. H. (2014). Expression of key transporters in the gill and esophageal-gastrointestinal tract of euryhaline Mozambique tilapia Oreochromis mossambicus acclimated to fresh water, seawater and hypersaline water. PLoS One 9(1):e87591. doi: 10.1371/journal.pone.0087591.

13. Hiong, K. C., Ip, Y. K., Wong, W. P. and Chew, S. F. (2014) Brain Na+/K+-ATPase α-subunit isoforms and aestivation in the African lungfish, Protopterus annectens. J. Comp. Physiol. B. 184:571–587.

14. Chew, S. F., Hiong, K. C., Lam, S. P., Ong, S. W., Wee, W. L., Wong, W. P. and Ip, Y. K. (2014). The roles of two branchial Na+/K+-ATPase α-subunit isoforms in salinity acclimation and active ammonia excretion in the giant mudskipper, Periophthalmodon schlosseri. Front. Physiol.5:158. doi: 10.3389/fphys.2014.00158.

15. Ching, B., Ong, J. L. Y., Chng, Y. R., Chen, X. L., Wong, W. P., Chew, S. F. and Ip, Y. K. (2014) L-gulono-γ-lactone oxidase expression and vitamin C synthesis in the brain and kidney of the African lungfish, Protopterus annectens. FASEB J. 28: 3506-3517.

16. Chng, Y. R., Ong, J. L. Y., Ching, B., Chen, X. Lo., Wong, W. P., Chew, S. F. and Ip, Y. K. (2014). Molecular characterization of argininosuccinate synthase and argininosuccinate lyase from the liver of the African lungfish Protopterus annectens and their mRNA expression in the liver, kidney, brain and skeletal muscle during aestivation. J. Comp. Physiol. B 184: 835-853.

17. Lam, S. H., Lui, E-Y, Li, Z., Cai, S., Sung, W-K, Mathavan, S., Lam, T. J., and Y. K. Ip. (2014). Differential transcriptomic analyses revealed genes and signaling pathways involved in iono-osmoregulation and cellular remodeling in the gills of euryhaline Mozambique tilapia, Oreochromis mossambicus. BMC Genomics 15:921DOI: 10.1186/1471-2164-15-921.

18. Chew, S. F., Hiong, K. C., Lam, S. P. and Ip, Y. K. (2015). Branchial Na+:K+:2Cl- cotransporter is involved in active ammonia excretion and seawater acclimation in the giant mudskipper, Periophthalmodon schlosseri. J. Comp. Physiol. B 185:57–72.

19. Ong, J. L. Y., Woo, J. M., Hiong, K. C., Ching, B., Wong, W. P., Chew, S. F. and Ip, Y. K. (2015). Molecular characterization of Betaine-homocysteine methyltransferase 1 from the liver, and effects of aestivation on its expressions and homocysteine concentrations in liver, kidney and muscle, of the African lungfish, Protopterus annectens. Comp. Biochem. Physiol. B 183:30-41.

20. Ching, B., Chew, S. F. and Ip, Y. K. (2015) Ascorbate synthesis in fishes: A review. IUBMB Life. In press.

21. Hiong, K. C., Ip, Y. K., Wong, W. P., and Chew, S. F. (2015). Differential gene expression in the liver of the African lungfish, Protopterus annectens, after 6 months of aestivation in air or 1 day of arousal from 6 months of aestivation. PLoS ONE. In press.

22. Garofalo, F., Amelio, D., Icardo, J. M., Chew, S. F., Tota, B., Cerra, M. C. and Ip, Y. K. (2015). Signal molecule changes in the gills and lungs of the African lungfish Protopterus annectens, during the maintenance and arousal phases of aestivation. Nitric Oxide. In press.

23. Ching, B., Woo, J. M., Hiong, K. C., Boo, M. V., Choo, C. Y. L., Wong, W. P., Chew, S. F. and Ip, Y. K. (2015). Na+/K+-ATPase α-subunit (nkaα) isoforms and their mRNA expression levels, overall Nkaα protein abundance and kinetic properties of Nka in the skeletal muscle and three electric organs of the electric eel Electrophorus electricus. PLoS One. In press.

24. Chew, S. F., Ching, B., Chng, Y. R., Ong, J. L. Y., Hiong, K. C., Chen, X. L., and Ip, Y. K. (2014). Aestivation in African lungfishes: physiology, biochemistry and molecular biology. In: G. Zaccone, K. Dabrowski, M.S. Hedrick, JMO Fernandes, J.M. Icardo (Eds.), Phylogeny, Anatomy and Physiology of Ancient Fishes. CRC Press. In press.

25. Ip, Y. K., Ching B., Hiong, K. C., Choo, C. Y. L., Boo M. V., Wong, W. P., and Chew, S. F. (2015) Light induces changes in activities of Na+/K+-ATPase, H+/K+-ATPase and glutamine synthetase in tissues involved directly or indirectly in light-enhanced calcification in the giant clam, Tridacna squamosal. Frontier in Physiology. Submitted.