Mechanism through which an anti-aging natural compound extends longevity of yeast by remodeling cellular lipid dynamics

The fundamental mechanisms of aging are conserved from yeast to humans. We use the yeast Saccharomyces cerevisiae as a model system with which to study the molecular mechanisms of aging. Our high-throughput chemical genetic screen of extensive compound libraries has identified lithocholic acid (LCA), a bile acid, as a potent anti-aging and anti-cancer compound (Aging (2010) 2:361-370). We found that LCA extends longevity of chronologically aging yeast.

Computational study into the stabilizing interactions in internal loops of oligonucleotides

Our focus in this computational proposal is on weak bonding interactions (WBIs) in the organization of molecular assemblies, here in particular oligonucleotides. With regards to WBIs, the hydrogen bond is certainly the most recognized, but C-H...O, C-H...pi, pi...pi and others must not be ignored if organization and stability are to be understood. WBIs are thus of fundamental importance in diverse phenomena, such as the effect of ligand-binding in ribonucleic acids on gene expression (riboswitches, mostly through pi...pi interactions).

Dehydrobenzooxepanes by Tandem Nicholas Reactions

Benzo- fused seven membered ring ethers, or benzooxepanes, are widely encountered structures within natural products such as the heliannuols. We intend to target the synthesis of this ring system by of employing derivatives of butyne-1,4-diol-Co2(CO)6 complexes, by way of tandem Nicholas reactions with para- substituted phenols, thereby constructing the seven- membered ring system.

Development and testing of crops demonstrating improved biomass hydrolysis for biofuel production

Biobased products, mostly derived from plant biomass, have the potential to improve the sustainability of Canada’s natural resources and environmental quality while competing economically. Plant biomass, composed primarily of cell walls and modification of cell wall properties has the potential to improve biomass conversion to biobased products such as biofuels. Progress towards achieving this goal is currently impeded by a lack of knowledge of how cell walls are assembled and how their structure affects the processing of biomass.

Role of 5alpha-Dihydrotestosterone and Androgen Receptor in Estrogen Receptor-Positive Breast Cancer

Breast cancer is the most frequent cancer affecting women, with 1 in 9 Canadian females expected to develop the disease in their lifetime. About 90% of estrogen receptor (ER)-positive breast cancers express androgen receptor (AR). Recent results in our laboratory demonstrated that the inactivation of 5alpha-dihydrotestosterone (DHT), the most potent androgen, contributes to estrogen-dependent breast cancer cell growth, and suggested additional pathways for DHT action in addition to the AR pathway. Our focus is to elucidate the role of AR and DHT in ER-positive breast cancer.

The study of action mechanism of indoles in Breast Cancer and Prostate Cancer

The indole subunit is a near-ubiquitous component of biologically active natural has become an important building block or intermediate in the synthesis of many pharmaceutical agents. Such as indole-3-carbinol, found in cruciferous vegetables has been shown to inhibit carcinogenesis. In this project I will focus on studying of action mechanism (cell apoptosis, angiogenesis inhibition and inhibiting microtubule formation) of indoles in breast cancer and prostate cancer. Establishment of models for the screening of indoles resources for resistance to breast and prostate cancer.

Eye Tracking as a functional biomarker in Neurological and Mental Health Disease

There is an urgent need for the development of new tools that can provide a relatively highthroughput, objective assessment of brain function in individuals with neurodevelopmental, neurodegenerative or psychiatric disorders. The overarching objective of this research proposal is to use eye movement tasks to identify biomarkers that can be used in the assessment of brain function in these disorders. We will utilize the EyeLink 1000 manufactured by SR Research Inc.

Fluorescence Correlation Spectroscopy as a tool to study the transcription rate of Bicoid targets during Drosophila embryonic development

In embryos, cell differentiation occurs via the formation of spatial gradients of molecules called morphogens, which control the expression of a number of target genes determining cell identity. A common model system to study morphogen is the Bicoid gradient, which determine anterio-posterior patterning in the Drosophila fly.

Evaluation of Tristetraprolin in a Lipopolysaccharide-induced mouse model of fetal loss

Maternal complications such as miscarriage or fetal loss are important reproductive issues that can affect up to 30% of pregnant women worldwide. While these complications are worldwide health problems, their mechanisms are not yet clear. Using a well-established mouse model of fetal loss, our goal is to detect localization patterns of important genes that may play a role in fetal loss. We also aim to detect and measure expression levels of these genes in the same samples as well.

Yeast Mitochondrial Threonyl-tRNA Synthetase (MST1) as a Model Enzyme for Studying High Fidelity Information: a Multi-scale Computational Chemistry Study

In order for the body to function properly, information from DNA must be translated correctly into proteins. One group of enzymes critical to this process is the aminoacyl-tRNA synthetases (aaRS). These enzymes attach an amino acid to its cognate tRNA, which delivers them to make proteins. Although this process is critical to the survival of the organism, the details of how the cell achieves such high fidelity and error-free task is not completely understood. Since some amino acids are so similar to each other, aaRS must be able to remove incorrectly attached amino acid-tRNA pairs.

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