2012 bioinformatics projects in Arkansas:

Avian Diseases

The Rhoads laboratory is using Next Gen Sequencing (NGS) to identify genes and gene networks involved in development of genetic diseases affecting chickens: Pulmonary Hypertension Syndrome, and Sperm Mobility. The chicken is being used as a medical model to understand these complex traits in humans. RNAseq is being applied to the testis and primordial germ cell transcriptomes. This information, along with analyses of the total proteome of sperm cells, is identifying key components in energy metabolism as critical to sperm mobility and fertility. Similar approaches to gene networks in lung arterioles is being applied to hypertension. Key regulatory genes in vasoconstriction have been identified. Genome resequencing is being used to identify the specific genetic alterations that lead to both traits. Additionally, we are using RNAseq to further define novel RNAs produced in the chicken reproductive tract. Bioinformatics components in these projects include analysis of NGS data for RNAseq, template based genome assembly, transcriptome assembly, genome annotation, and web based genome browsers.

Website: http://www.uark.edu/ua/drhoads

Pre-requisite courses: Cell Biology; Genetics

Principal Investigator: Douglas Rhoads, Ph.D.
Professor, Biological Sciences
University of Arkansas

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Functional role of protein deamidation

Non-enzymatic deamidation (DA) of asparagines and glutamines irreversibly introduces negative charge into proteins. In this respect DA is similar to enzymatic phosphorylation (although phosphorylation is reversible), and Asp is frequently used as phosphomimetic in site-directed mutagenesis studies (e.g. Ser–>Asp mutation). DA has been long recognized as protein damage – accumulating with age in long-lived proteins such as lens crystallins. DA has been associated with aging, exposure to environmental toxins, smoking, and disease. One would expect dramatic changes in protein function upon deamidation, similar to phosphorylation – yet such examples of functional deamidation, beyond loss of function – are scarce. Importantly, while non-enzymatic, rate of DA is highly dependent on protein primary and secondary structures, with life-times spanning the range from hours to hundreds of years. The hypothesis of this study is that in certain irreversible biological processes, deamidating proteins can serve as timers, triggering time-specific functional response.

The goal of this project is to test this hypothesis, by scanning sequences of enzymes from the organisms with sequenced genomes, containing catalytic aspartates/ glutamates, and finding their homologs, which have asparagines/glutamines instead of the catalytic acidic residues. We will start examining serine proteases, which require catalytic aspartate for their function. Are there close-related homologs, but with asparagines? Such proteins are expected to be inactive, but will become active (gain of function) after deamidation – either at certain a time-point in an organism life, or in response to change in environment. Upon project success we will extend this approach to other enzymes relying on Asp/Glu chemistry, such as c-rings of ATP-synthases, etc.

Principal Investigator: Galina Glazko, Ph.D.
Assistant Professor, Biomedical Informatics
University of Arkansas for Medical Sciences