A Bioinformatics Approach for Investigating Genes Involved in Dopaminergic Function and Degeneration

Undergraduate #74
Discipline: Biological Sciences
Subcategory: Computer Science & Information Systems

Sharee N. Brewer - Fisk University

Caenorhabditis elegans (C. elegans), is a powerful model system for biological studies and inquiry. Though this organism is relatively simple (with only about 1000 somatic cells in the hermaphrodite form), much of its molecular and cellular function is homologous to that of Homo sapiens. Understanding the molecules present in the various cell types of this nematode worm can give insight into the analogous cells in humans. In order to gain insight into relationships from C. elegans gene expression datasets, I used Python (version 2.7) to develop a program to automate the retrieval of information about C. elegans genes, known functions, and their human homologs. The goal was to link and retrieve information from the databases WormBase (www.wormbase.org) and Online Mendelian Inheritance in Man (www.omim.org) to compiled lists of selected C. elegans gene expression datasets. Doing this manually for many genes, to navigate and to decipher all of the information, would be very time-consuming and inefficient. As an initial test dataset, we used a list of over 1200 C. elegans genes whose expression was enriched in dopamine (DA) neurons (generated by Spencer et al., 2011). This program can now easily be applied to other large C. elegans gene lists, such as recently generated datasets from deep-sequencing of mRNAs (RNA-Seq) performed in our lab.

In a related, but independent project, I am also analyzing dopamine neuron degeneration in C. elegans that have been exposed to copper. Patients with Parkinson’s disease (PD) not only have dopaminergic neurodegeneration, but also tend to have higher levels of metals (such as iron, copper, and manganese) in their systems. With the hypothesis that exposure to metal can lead to neurodegeneration associated with early onset of PD, my goal is to analyze the effect that copper has on dopamine degeneration in C. elegans, and find what genes are involved. Our findings may correlate with and provide insight into Parkinson’s disease and other diseases that involve dopaminergic neurodegeneration.

References: Montes, Sergio et al. ‘Copper and Copper Proteins in Parkinson’s Disease.’ Oxidative Medicine and Cellular Longevity 2014 (2014): 147251. PMC. Web. 17 June 2015.
Online Mendelian Inheritance in Man. John Hopkins School of Medicine, 1985. Web. 2 June 2015.
WormBase. WS247. National Human Genome Research Institute, 1999. Web. 2 June 2015

Funder Acknowledgement(s): I thank Dr. Lei Qian, Dr. Brian Nelms, Dr. Sanjukta Hota, the participants of the Bioinformatics and Biomathematics summer program, and the members of the Nelms’ lab for their aid, support, and encouragement. Funding was provided by NSF HBCU-UP Targeted Infusion Project (HRD#1332491).

Faculty Advisor: Brian Nelms,