Reversible paralysis has been successfully used in Drosophila to genetically dissect the proteins necessary for proper development and function of the nervous system. In particular, we study a class of genes in Drosophila known as bang-sensitive paralytics. When a detrimental change or mutation is made in any one of genes, the flies carrying these mutations seize and paralyze in response to mechanical shock. These flies also display seizures, failures and abnormal facilitation in physiological recordings. We are interested in studying these genes at a systems level and a molecular level to find out what neural processes are defective in these mutants. Studies in the lab utilize many techniques: biochemical, pharmacological, molecular genetic, physiological and behaviorial analyses. Evidence gathered so far indicates that these genes are involved in development of the molecular characteristics of specific neurons, and in maintaining the electrical properties of the neuron. Our research on these mutants has applications in the fields of learning and memory, aging, epilepsy and human neurodegenerative disease.
Anatomy of bang-sensitivity
One project currently underway in the laboratory is a study to determine what parts of the nervous system are involved in bang-sensitive (bs) behavior. If we can determine the circuitry involved we can then use the fly as a model for seizure disorders like epilepsy. One approach to this problem is to look at the expression of the bang-sensitive genes. We have used reporter gene constructs and in situ hybridization to localize the RNA products of the genes. The photo at the right shows bs gene expression in the fly's head using one of these reporter constructs. In another set of studies we have used simple surgeries and behavioral tests to determine what sensory input triggers bs behavior. These studies point to the antennae as the source of input triggering the behavior and the antennal circuits as involved in generating behvaior. Some additional molecular genetic experiments are underway to confirm this hypothesis.
Some examples of student studies:
- Nicholas Trotta (Biology, '00) Cell-specific expression of the easily-shocked gene in Drosophila , Excel Scholar, Independent Research, Summer 1998-Spring 2000. Nick is now enrolled at Vanderbilt University in the Ph.D. program in Neuroscience.
- Kate Devlin (Biology, '03) An exploration of the neural locus of bang-sensitivity in the Drosophila brain, Independent Research, Fall 2002-Spring 2003. Kate is now a research technician at the University of Pennsylvania.
- Stephen Tanner (Neuroscience, '04), Localization of bang-sensitive behavior within the Drosophila nervous system, Excel Scholar, Honors Thesis research, Summer 2003 - current.
Pharmacological analysis of bang-sensitivity
We have used various drugs that are used to treat human epilepsy (AED's) to compare fly bang-sensitivity to human seizures. The drugs can also be used to explore which physiological properties of bs circuits are defective. We can look at the effects of drugs by measuring the length of time individual flies (or fly populations) display seizure or paralytic behaviors or by looking at the electrophysiology of a representative neuronal circuit.
Some examples of student studies on the effects of AED's on bang-sensitive behavior in Drosophila melanogaster:
- Carol McKeever (Biology, '00) AED acute effects, Independent Research, Fall 1999-Spring 2000, currently in law school.
- Ben Jacobs (Biology, '01) Dilantin, Independent Research, Spring-Fall 2000. Now enrolled in UMDNJ Dental School.
- Eric Stauffer (Neuroscience '02) Dilantin physiology, Excel, Independent Research, Summer 2001-Spring 2002. Now enrolled in the University of Virginia, Ph.D. program in Neuroscience.
- Laura Feeney (Behavioral Neuroscience, '02) Gabapentin, Excel, Spring 2001-Spring 2002. Now enrolled in the Thomas Jefferson University Physical Therapy MS program.
- Elizabeth Rojan (Biology, '03) Gabapentin, Excel, Independent Research, Summer 2002-Spring 2003. Now a research technician at Johns Hopkins University.
Bang-sensitivity and mitochondria
Two of the bs mutants have gene products that are found in the mitochondria. There is some evidence that in these two mutants and maybe another, the mitochondria are not operating properly and that this leads to bs behavior. The bs mutants can thus be used as a model system to look at the role of the mitochondria in nervous system function.
Analysis of mitochondria in bang-sensitive neurons:
- Jason Cromer (Computer Science, '01) Distribution of mitochondria in wildtype and bs strains of Drosophila, Excel Scholar, Fall 2000-Spring 2001. Now enrolled in the University of Connecticut Ph.D. program in Neuroscience.
- Erin Wolfson (Neuroscience, '05) Mitochondrial structure defects in bs mutants of Drosophila, Independent Research, Spring 2003-current.
Shortened lifespan and other age-related defects in bang-sensitive mutants:
- Brooke Keim (Biology, '03) Shortened lifespan and other age-related defects in bang-sensitive mutants of Drosophila, Excel Scholar, Honors Thesis, Spring 2002-Spring 2003. Now enrolled in the Medical School of Temple University.
Recent published abstracts (*indicates Lafayette students)
- Trotta*, N.C., Martin*, L.A. and Reynolds, E.R. (2000). Cell-specific expression of the bang-sensitive paralytic gene, easily shocked A. Conf. Dros. Res. 41: 777B.
- Martin*, L.A., and Reynolds, E.R. (2000). Tissue-specific expression and genetic interaction of bang-sensitive paralytic mutants. J. Penn. Acad. Sci. (Abstract and Index Issue) 73: 168.
- Trotta*, N.C., and Reynolds, E.R. (2000). Cell-specific expression and retinal
defects associated with dosage in the Drosophila bang-sensitive paralytic gene easily shocked. J. Penn. Acad. Sci. (Abstract and Index Issue) 73: 181.
- Nyako*, M., and Reynolds, E.R. (2000). Analysis of ethanolamine kinase activity throughout the D. melanogaster lifecycle. J. Penn. Acad. Sci. (Abstract and Index Issue) 73: 171.
- Mckeever*, C., Kelly*, H., and Reynolds, E.R. (2000). Effects of human epileptic drugs on bang-sensitive mutants of Drosophila melanogaster. J. Penn. Acad. Sci. (Abstract and Index Issue) 73: 169.
- Reynolds, E.R., Nyako*, M., Marks*, C., and Sherma, J. (2001). Ethanolamine kinase activity and lipid composition in wildtype and bang-sensitive mutants. A. Conf. Dros. Res. 42: 849C
- Cromer*, J., and Reynolds, E.R. (2001). Distribution of mitochondria in wildtype and bang-sensitive strains of Drosophila melanogaster. J. Penn. Acad. Sci. (Abstract and Index Issue) 74: 125.
- Ickowicz*, J., and Reynolds, E.R. (2001). Expression of technical knockout, a bang-sensitive gene in Drosophila melanogaster. J. Penn. Acad. Sci. (Abstract and Index Issue) 74: 134.
- Reynolds, E. R., Feeney*, L., Stauffer*, E., Jacobs*, B., Kelly*, H., and
McKeever*, C. (2001). Human epileptic drugs reduce seizure and paralysis in
easily shocked, a bang-sensitive mutant. Abstracts of papers presented at
the 2001 meeting on Neurobiology of Drosophila, October 3-7, 2001. Bellen,
Taylor, 2001 2001:48.
- Reynolds, E. R., Stauffer*, E., Feeney*, L., Jacobs*, B., Kelly*, H., and
McKeever*, C. (2002). Human epileptic drugs reduce seizure and paralysis in
bang-sensitive mutants. A. Conf. Dros. Res. 43: 845B.
- Feeney*, L., Jacobs*, B., and Reynolds, E. R., (2002) Antiepileptic drugs reduce seizure and paralysis in Drosophila bang-sensitive mutants." Poster presentation at the National Conference for Undergraduate Research in Whitewater, WI, April 24-28, 2002.
- Stauffer*, E.A., Feeney*, L., Jacobs*, B., and Reynolds, E. R. (2002). Antiepileptic drug action in a Drosophila model of epilepsy. 2002 Abstract Viewer/Itinerary Planner. Washington DC: Society for Neuroscience, Program No. 797.7.
- Reynolds, E.R., Keim*, B., and O'Brien*, K. (2003). Shortened lifespan and other age-related defects in bang-sensitive mutants. A. Conf. Dros. Res. 44: 738C.
- Devlin*, K., and Reynolds, E.R. (2003). An exploration for the neural locus of bang-sensitivity in the Drosophila brain. J. Penn. Acad. Sci. (Abstract and Index Issue) 76: 114.
- Ingersoll, E.P., Martin, A. J., Lacoff*, L., and Reynolds, E.R. (2003).
Aminopeptidase N activity is reduced in Drosophila slamdance mutants. J. Penn. Acad. Sci. (Abstract and Index Issue) 76: 125.
Recent Publications:
- Wang, X., Reynolds, E.R., Deak, P., and Hall, L.M. (1997). The seizure locus encodes the Drosophila homologue of the HERG potassium channel. Journal of Neuroscience 17 (3): 882-890.
- Nyako*, M., Marks*, C., Sherma, J. and Reynolds, E.R. (2001) Tissue-specific and developmental effects of the easily shocked mutation on ethanolamine kinase activity and phospholipid composition in Drosophila melanogaster. Biochemical Genetics 39(9-10): 339-349.
- Reynolds, E. R., Graceffa*, L., and Majumdar, S.K. (2001) Effects of Neem-Based Bioactive Compounds on the Development of Three Laboratory Strains of
Drosophila melanogaster (Diptera: Drosophilidae). International Journal of Ecology and Environmental Science 27: 147-154.
- Zhang, H., Tan, J., Reynolds, E., Kuebler, D., Faulhaber, S., and Tanouye, M. (2002). The Drosophila slamdance gene: a mutation in an aminopeptidase can cause seizure, paralysis and neuronal failure. Genetics 162: 1283-1299.
- Reynolds, E.R., Stauffer*, E.A., Feeney*, L., Rojahn*, E., Jacobs*, B., and
McKeever*, C. (2003). Treatment with the antiepileptic drugs phenytoin and
gabapentin ameliorates seizure and paralysis of Drosophila bang-sensitive
mutants. In press, Journal of Neurobiology.
Manuscripts submitted or in preparation:
- Trotta*, N.C., Martin*, L.A., Stauffer*, E., and Reynolds, E. R. Tissue-specific expression of the easily shocked gene. Submitted to Journal of Neurogenetics.
- Devlin*, K., Rojahn*, E., Tanouye, M. and Reynolds, E.R. Genetic and behavioral analysis of the bangsenseless gene of Drosophila melanogaster.
- Keim*, B., Tanner, S., and Reynolds, E.R. Shortened lifespan and other age-related defects in bang-sensitive mutants.
Updated 8/03.
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