MOL BIO COLLOQUIUM
March 11, 2022
ELISHA DAVID ADAUI
Cooperative olfaction in the Zika mosquito Aedes aegypti
Olfaction is a critical sense for animals. Its functional units are the chemical-binding chemoreceptors expressed in olfactory sensory neurons. The synapses between these neurons with second order neurons form spherical glomeruli in the brain. Mouse and fly model organisms exhibit a 1 chemoreceptor to 1 olfactory sensory neuron to 1 glomerulus correspondence. Several lines of evidence suggest that the Zika mosquito Aedes aegypti does not follow this canonical model and instead expresses multiple chemoreceptors in a single neuron. Leveraging the power of singleomics, I demonstrate that indeed the olfactory chemoreceptive architecture of the deadliest animal in the world is cooperative rather than individual.
Epitranscriptomic regulation plays important roles in normal liver maintenance as well as response to injury and viral infection
RNA modifications play important roles in gene regulation. N6-methyladenosine (m6A) is the most common RNA modification and the most well studied but the extent of the impacts of m6A modification have not been thoroughly studied in vivo: literature concerning m6A in the liver largely focuses on disease states, and there are few in-vivo studies. I have created mouse lines with constitutive or inducible knockout of the readers and writers of m6A modification, and my preliminary data suggest that while m6A regulation may not be essential for liver development, disruption of normal m6A modification in hepatocytes leads to progressive liver damage resulting in fibrosis. Models of liver injury and regeneration further show that m6A recognition plays crucial roles in functional liver regeneration and injury response. Transgenic expression of hepatitis B virus leads to further liver inflammation and fibrosis in mice with m6A deficient hepatocytes. Experiments using Hepatitis C virus entry-permissive mice are also underway to determine the in vivo impact of m6A on HCV RNA longevity in hepatocytes. Changes in histopathological findings and RNA sequencing, among other metrics, are beginning to reveal the extent of the impact and role of m6A modification and recognition in the liver. In order to analyze the specific mechanisms leading to these changes, we are working to implement tools which will allow transcript-specific demethylation of m6A sites, allowing us to confirm whether m6A modification is directly responsible for the expression level changes seen in m6A dysregulated mice.