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44 researchprogram in molecular physiologyDIRECTORPeter J.S. SmithPROGRAMADMINISTRATORTiffany Van MooyADJUNCT SCIENTISTSAyse Dosemici, NNDS,NIH, BethesdaMiguel Holmgren, NNDS,NIH, BethesdaGeorge Holz, New YorkUniversityRon Pethig, Universityof Northern WalesBIOCURRENTSRESEARCH CENTERDIRECTORPeter J.S. SmithPROGRAMADMINISTRATORTiffany Van MooyRESEARCH ASSISTANTSCIENTISTSMark MesserliEmma HeartPOSTDOCTORALSCIENTISTSLeon CollisDamon OsbournAnthony MolinaRESEARCH ASSOCIATERichard SangerBROWN UNIVERSITYROTATIONLorin JakubekRESEARCH ASSISTANTSDaniel BogorffErica CorsonCraig HamiltonRobert LewisGRAPHICS ANDDATABASE DEVELOPERTamara ClarkINFORMATICSDave RemsenSUMMER INTERNJames PringleLABORATORY OFROBERT GREENBERGASSOCIATE SCIENTISTRobert GreenbergPOSTDOCTORALSCIENTISTShanta MesserliJoseph ConsiglioRESEARCH ASSISTANTChristine EvolaWill MorganThe goal of the Program in Molecular Physiology (PMP) is to advance our knowledgeof basic and biomedical problems through the study of cellular dynamics in the livingcell. Most of the work being done focuses on physiological and transport dynamics atthe molecular, cellular, and systemic level. An important component of these studies isthe development and application of advanced techniques for the detection of specificmolecules and structures. This is largely the activity taking place in the BioCurrentsResearch Center (BRC), a significant part of the Program funded by the National Centerfor Research Resources (NCCR:NIH). This work follows a long and successful traditionwithin the MBL community for the non-invasive study of living cells, notably pursuedby Shinya Inoué and Rudolf Oldenbourg of the Architectural Dynamics Program, aleading component of cell sciences at the MBL. The focus of the research within theBRC group and our collaborators is the use of boundary layer electrochemistry to detectthe transport of selected solutes across the plasma membrane. This research programcontinues to offer access to advanced electrochemistry, electrophysiology, and imagingtechniques—the latter includes low light and luminescent, as well as spinning discconfocal. The laboratory of Robert Greenberg, the second major component of thePMP, is working to better understand the neuromuscular system of schistosomes atthe molecular level, with an eventual goal being to provide possible molecular targetsfor new, potent and specific antiparasitic agents. Schistosomes, or blood flukes, areflatworms that parasitize humans and cause schistosomiasis, a widespread tropicaldisease that affects approximately 200 million people, killing as many as 280,000 peopleper year. Greenberg’s lab brings a strong molecular perspective to the program, as wellas a very interesting biological challenge.Over the past year Greenberg’s group has continued to study voltage-gated calciumchannels (VGCCs) from schistosomes, which express a VGCC β subunit subtypewith unique structural and functional characteristics, including the ability to conferpraziquantel sensitivity to VGCCs that normally do not respond to the drug. This βsubunit is also unique because it lacks two highly conserved consensus protein kinase Cphosphorylation sites in a critical region of the protein. They have proposed that thosemissing sites are determinants of the unusual functional properties and pharmacologicalsensitivities of this β subunit, and are using site-directed mutagenesis to test thathypothesis. Several other biophysical and molecular aspects of this channel are alsobeing studied. In addition to this work, Greenberg and colleagues are examining nitricoxide (NO) regulatory pathways in schistosomes. To date, they have demonstrated thepresence and distribution of nitric oxide synthase immunoreactivity and enzymaticactivity in adult schistosomes. Using fluorescent probes, they have demonstrated theproduction and distribution of authentic NO in living worms. Currently, this aspectof Greenberg’s work is developing the use of high-throughput methods to defineNO-responsive genes in schistosomes. This part of the study is being pursued incollaboration with Andrew McArthur of the Bay Paul Center.