Jennifer Gallagher, Ph.D.
Why are individuals from a population different from each other? The genetic makeup of a population is stratified so that the individuals survive and continue the species when challenged by different environments. To understand which genetic differences matter the most between individuals in response to environmental challenges, we address these questions in the laboratory using yeast as a model organism. What can a single cell organism teach us about how individuals are suited for their environments? Yeast is a single celled eukaryote with a compact sequenced genome. Different strains of yeast are individuals in a population. There is more genetic diversity between two strains as there is between two human individuals. Using this wealth of genetic diversity, we can ask which kind of genes vary and how that variation influences response to different chemicals.
This genetic variation can be in the form of polymorphisms in coding regions, non-coding regions and regulatory elements, and copy number variation. Genetic variations in transcription factors and their binding sites can change gene regulatory networks allowing rapid adaption to new environments and provides insights into molecular mechanisms of these pathways. These changes in gene regulatory networks alter transcription and the cellular proteome, ultimately impacting an organism’s response to stresses and disease. Future experiments will explore how different chemicals such as chemotherapeutic drugs, hydrocarbons from mining and food additives affect cellular pathways.
Dr. Gallagher's lab uses high throughput genomics, transcriptomics and proteomics to address the impact of genetic diversity on cellular mechanisms within a species.
Systems biology addresses the cell as a whole by not focusing on a gene or one pathway; it instead incorporates new technologies to understand biological networks. As limits of detection in proteomics decrease exponentially, new questions in genomics and transcriptomics can be addressed. The correlation between levels of the transcriptome and the proteome is around r=0.4-0.7, depending on the method of measurement. Is there biological significance to the mRNAs whose levels are different than its protein level? The cells may contain a store of untranslated mRNAs to be used for coping with different environments. Cells can be faced with challenging conditions rapidly and these mRNAs could be ready to be translated in a moment notice. The cells could sequester these mRNAs in stress granules. Stress granules are amorphous RNA-protein bodies that have been difficult to biochemically purify and study.