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Investigating C. elegans Dopamine Neuron-Enriched Genes Linked to Human Disorders

Undergraduate #91
Discipline: Biological Sciences
Subcategory: Genetics

Jiah Toms - Fisk University
Co-Author(s): CCorey Roach, Jennifer Quinde, and Brian Nelms, Fisk University, Nashville, TN



Dopamine is a neurotransmitter that controls the central nervous system, including motor control, cognition, and reward pathways. Studies have shown an association between disruption of dopamine-producing neurons and human disorders, such as Parkinson’s Disease, ADHD, Drug Addiction, Schizophrenia, and Depression. Parkinson’s disease specifically is associated with a progressive loss of dopamine neurons and reduced dopamine signaling, resulting in muscular rigidity, slow imprecise movement, and irregular blood pressure. The purpose of my research is to determine the correlation between genes, the Nelms lab has identified through RNA-sequencing to be highly expressed in C. elegans dopamine neurons, and dopamine neuron functions and relationships to human disorders. We use C.elegans as a model because of the conservation of genes and molecular processes between worms and humans. The genes that relate to dopamine and human disorders can then be tested in C. elegans to ascertain their functions. I have examined a list of 534 differentially expressed genes generated by comparing RNA-Seq data from isolated dopamine neurons and whole worms. I have used several bioinformatics tools to collect more information on their homology and predicted functions. Some candidate genes that we have identified encode a complexin (CPX) protein, fatty acid amide hydrolase (FAAH), GTPase-activating protein SynGAP, and a ubiquitin carboxyl-terminal hydrolase (UCHL). I have tested a deletion mutant of the C. elegans gene cpx-1 and have found that it displays a dopamine-related swimming-induced paralysis defect. I plan to further characterize the role of this gene in C. elegans dopamine neurons. From this research we hope to gain insight into dopamine neuron genes that are relevant for human disorders.

Funder Acknowledgement(s): NSF HBCU-UP Research Initiation Award #HRD 14-01091/ NIH BD2k R25 Grant Fisk-ULUC Bioinformatics/ NSF-TIP #1332491.

Faculty Advisor: Brian Nelms, BNELMS@FISK.EDU

Role: I investigate genes within a data set obtained from C.elegans cell-specific RNA-sequencing experiments in the Nelms lab. I used bioinformatics tools to determine a correlation between dopamine neuron enriched genes and human disorders. From there, I tested cpx-1 strain and found that dopamine is highly expressed by conducting a swimming induced paralysis assay.

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This material is based upon work supported by the National Science Foundation (NSF) under Grant No. DUE-1930047. Any opinions, findings, interpretations, conclusions or recommendations expressed in this material are those of its authors and do not represent the views of the AAAS Board of Directors, the Council of AAAS, AAAS’ membership or the National Science Foundation.

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