The long-term goal of the Scientific Core is to promote independent scientific and clinical hypothesis building and experimental and clinical testing for Peruvian and Sri Lankan scientists. This Scientific Core will facilitate achieving this long-term goal and the success of the two research projects by enhancing research capacity building in Peru (Research Project 1) and Sri Lanka (Research Project 2). The hypotheses to be tested in the Scientific Core include the following: 1) The infecting Leptospira in Peru and Sri Lanka are diverse and can be identified by MLST in infected patient blood and urine specimens; the Scientific Core can coordinate necessary DNA sequencing; 2) There will be novel Leptospira species, serovars and strains obtained in Peru and Sri Lanka that require advanced molecular and genomic analysis, with technical support for the foreign collaborative teams provided by the Scientific Core; 3) Serologies performed at central governmental reference laboratories in Peru and Sri Lanka are inaccurate or inadequate, as suspected by both Research Project Leaders and the Program Director; 4) New diagnostic tests to diagnose leptospirosis using antibody detection will be more accurate by using Leptospira genomics-driven protein microarray technology; 5) New diagnostic tests to diagnose leptospirosis by detection of leptospiral antigens will add new accuracy using immunochemical techniques and monoclonal antibody development, to be coordinated with UC San Diego for macromolecular biophysical analytical work and with the mAb development company A&G Precision Antibodies.
The Specific Aims of the Scientific Core include the following: 1) To coordinate all work related to DNA sequencing from Sri Lanka (limited capacity exists in Peru but capacity will be supplemented as need in USA) for Multi Locus Sequence Typing (MLST) (Projects 1 and 2, Specific Aim 2); 2) To coordinate generation of whole genome sequencing of prioritized Leptospira isolates for genome analysis and workshop training (along with Administrative Core) (Projects 1 and 2, Specific Aim 2); 3) To train academic personnel from Peruvian and Sri Lankan universities to perform quality control on specimens with qPCR standardization; perform and monitor all immunological and molecular biology procedures (Projects 1 and 2, Specific Aim 1);To coordinate reference leptospiral serologies with the U.S. Centers for Disease Control (Projects 1 and 2, Specific Aim 1); and to train academic personnel from Peruvian and Sri Lankan universities to perform accurate serological analysis of leptospirosis patients in Peru and Sri Lanka; 4) To subcontract and coordinate multinational leptospiral protein microarray work with UC Irvine Projects 1 and 2, Specific Aim 3a); 5) To coordinate necessary advanced analytical work (mass spectrometry, HPLC glycobiology) at UCSD (Projects 1 and 2, Specific Aim 3b); 6) To subcontract and coordinate monoclonal antibody production and biophysical selection of high affinity antigen capture/detection v pairs with A&G Precision Antibody, Columbia, MD which will be deployed to Peru and Sri Lanka for their respective research projects (Projects 1 and 2, Specific Aim 3b).
| Agampodi, Suneth B; Dahanayaka, Niroshan J; Nöckler, Karsten et al. (2016) Redefining Gold Standard Testing for Diagnosing Leptospirosis: Further Evidence from a Well-Characterized, Flood-Related Outbreak in Sri Lanka. Am J Trop Med Hyg 95:531-6 |
| Fouts, Derrick E; Matthias, Michael A; Adhikarla, Haritha et al. (2016) What Makes a Bacterial Species Pathogenic?:Comparative Genomic Analysis of the Genus Leptospira. PLoS Negl Trop Dis 10:e0004403 |
