Ph.D. Princeton University.Research Interests
The dawn of the 21th century can be characterized as the golden era in biochemistry, as much as the dawn of the 20th century was the golden era for physics. In 2003, we witnessed the complete sequencing of human DNA (genome) and we now have access to many mammalian, plant and microbial genomes. An important scientific challenge for the 21st century is interpreting the vast amounts of DNA sequence data that has become available. A portion of these sequences encode for proteins, which are nature’s ‘nanomachines’. These are the workhorses in a cell, and they have been exquisitely designed to carry out cellular processes with remarkable efficiency and fidelity. Understanding the structure and function of these proteins is critical in converting the DNA sequence information that we now have, into tangible benefits to humankind - whether it be new protein targets for drugs, or perhaps more efficient enzymes for use in biotechnology. Research conducted in our laboratory focuses on the broad problem of interpreting DNA sequence data to obtain biologically meaningful information.
Identification of Disease-causing (virulence) Genes in the Corn Pathogen Fusarium verticillioides
Members of the genus Fusarium are economically important plant pathogens, that cause billions of dollars of damage each year worldwide. Fusarium verticillioides is known to cause destructive diseases in a wide variety of agriculturally important crops including corn, wheat and potato. In corn, it causes the disease knows as stalk rots. In this project, we focus on identifying and characterizing proteins associated with infectivity or virulence. This is done through an analysis of the recently-sequenced genome of F. verticillioides, using a combination of bioinformatics and experimental methods.
Predicting the Function of Proteins
Our second area of interest is in using bioinformatics tools developed by us, and others, to predict the function of proteins that are, as yet, not annotated, using just the information from the protein sequence. We have been focusing our attention on a set of protein sequences from the well-known database Pfam. These sequences belong to Pfam families known as ‘Domains of Unknown Function’ (DUF). Since Pfam is used extensively in annotating protein sequence data from genomes such as the human genome, determining the functions of DUFs will directly assist current efforts to decode sequences from genomes.
Development of Tools for Bioinformatics
In the past few years, we have been improving the most popular bioinformatics tool that is currently available, BLAST. We have been using our expertise in structural biology to incorporate protein structure data into BLAST, to significantly enhance its capability in annotating proteins through detection of remote homologs. We have now incorporated a context-specific amino acid substitution matrix into BLAST, to create CSSM-BLAST. CSSM-BLAST excels at detecting remote homologs to proteins of known structure. We are now pursuing our interests in developing a set of second-generation structure-based amino acid substitution matrices.
Collaborative Research Projects
1. Provide structural annotation to a protein that is associated with the nuclear pore complex, REA1 (Dr. R. Dhar and colleagues from the National Cancer Institute).
2. Isolation of disease resistance genes (R genes) conferring resistance to the fungus Fusarium verticillioides in corn (Dr. James Jurgenson of the Department of Biology).
3. Transcriptional profiling of drought tolerance of the reproductive structure s of barley (Dr. Tilahun Abebe of the Department of Biology).
Selected Publications
1. Schutt, C.E., Myslik, J.C., Rozycki, M.D., Goonesekere, N.C.W. and Lindberg, U. (1993) The Structure of profilin:actin at 2.55 angstrom resolution Nature 365 810.
2. Zeppezauer, E. S. C., Goonesekere, N.C.W., Rozycki, M.D., Myslik, J.C., Dauter, Z., Lindberg, U. and Schutt, C.E. (1994) The structure of profilin at 2.0 angstrom resolution J. Mol. Biol. 240 459.
3. *Goonesekere, N.C.W., Gunasekera, M.B. and Fernandopulle, N. (1999) Use of DNA typing For Criminal Casework in Sri Lanka. Proceedings of the 10th International Symposium on Human Identification Promega Corporation,Wisconsin, U.S.A..
4. *Tiedemann, R., Kurt, F., Goonesekere, N.C.W., Gunasekera, M.B., and Ratnasooriya, W.D. (1999) A simulation study on the viability of Sri Lankan elephant populations. Folia Zoologica 48 (supp. 1): 95-104.
5. *Fernandopulle, N., Gunasekera, M.B. and Goonesekere, N.C.W. (2002) Population genetics of eight STR loci from Sri Lanka. Forensic Science International 126 1 93.
6. *Vandebona, H., Goonesekere, N.C.W., Ratnasooriya, W.D., Alahakoon, J. and Gunasekera, M.B. (2002) The establishment of paternity of elephants born in captivity in Pinnawela Elephant Orphanage, Sri Lanka, by DNA fingerprinting. International Zoo Yearbook 39.
7. *Vandebona, H., Goonesekere, N.C.W., Tiedemann, R., Ratnasooriya, W.D., and Gunasekera, M.B. (2002) Sequence variation at two mitochondrial genes in the Asian elephant (Elephas maximus) population in Sri Lanka. Mammalian Biology 67 4 193.
8. *Mapatuna, Y., Gunasekera, M.B., Ratnasooriya W.D., Goonesekere, N.C.W. & Bates P.J.J. (2002) Unravelling the taxonomic status of the Genus Cynopterus (Chiroptera:Pteropodidae) in Sri Lanka by multivariate morphometrics and mitochondrial DNA sequence analysis Mammalian Biology 67: 321.
10. Goonesekere, N.C.W. and Lee B. (2004) Frequency of gaps observed in a structurally aligned protein pair database suggest a simple gap penalty function Nucleic Acids Research 32 9 2838.
11. De Silva, A.P., de Silva, S.S.K., Goonesekere, N.C.W. (2007) Gunaratne, H.Q.N, Lynch, P.L.M, Nesbitt, K.R., Patuwathavithana, S.T., Ramyalal, N.L.D.S. Analog Parallel Processing of Molecular Sensory Information. Journal of the American Chemical Society 129: 3050.
12. Goonesekere, N.C.W. and Lee B. (2008) Context-specific substitution matrices and their use in the detection of protein homologs. Proteins: Structure, Function and Bioinformatics 71: 910.
