Recent Findings

The CBD is staffed by upwards of 100 researchers including postdoctorals, graduate students, and undergraduates. Interactions with other Research Groups inside and outside of the LSI are numerous. A short summary of recent findings is given below:

Andersen. Using high throughput screening of marine sponge sediments and terrestrial actinomycete isolates, we have identified natural products of novel with a wide variety of biological activities.

Brayer. We are pursuing promising “hits” for novel antibiotics active against Gram–negative bacteria and mechanism-based therapeutics for diabetes and obesity. In addition a pioneering affinity-driven crystallization approach is being applied to the identification of novel cathepsin K inhibitors.

Bromme. Our studies of proteases implicated in atherosclerosis, bone and joint and autoimmune diseases have led to the identification of several promising low molecular weight inhibitors with novel binding sites.

Cullis. We have designed and are in the process of optimizing liposomal nanoparticle based delivery systems that will allow siRNA to be used therapeutically in vivo.

Davies. The isolation of actinomycete bacteria from BC lichens, liverworts and mosses numbers over 2000; these strains are providing a variety of novel bioactive compounds. Our studies of antibiotic resistant integrons from the environment have revealed many gene cassettes.

Eltis. We discovered a cholesterol degradation pathway in M. tuberculosis and are providing new insights into how these cholesterol-degrading enzymes function.  Collaboratively, we have established that M. tuberculosis metabolizes cholesterol during infection and that this metabolism is critical during the early stages of infection, contributing to the dissemination of the pathogen in the host.

McIntosh. Using NMR spectroscopy, new mechanisms for the regulation of ETS transcription factors by “bead-on-a-string” sumoylation and the “rheostatic” effects of multi-site phosphorylation on DNA-binding auto-inhibition were elucidated. This may provide a new approach to the understanding and treatment of ETS-related cancers.

Molday.  Using a wide variety of biochemical, molecular and cell biology techniques, we are studying molecular and cellular mechanisms responsible for a number of retinal degenerative diseases that are leading causes of vision loss.  These include X-linked retinoschisis, retinitis pigmentosa, Stargardt macular degeneration and others. The information obtained from these studies is being used to develop novel gene and drug based treatments in animal models for these diseases.

Numata. Organellar pH is tightly regulated within a narrow range, which plays a vital role in various physiological processes.  Our research group has identified novel binding proteins to organellar membrane type NHEs that contribute to organellar pH homeostasis.  Characterization of these binding proteins will lead to a better understanding of these ill-defined ion transporter functions in different cell types.

Roberge. We are using high throughput screening methods with both natural product and combichem libraries in collaboration with a number of other groups in areas of cancer chemical biology, cancer cell invasion and metastasis, mitotic progression, autophagy and drug discovery associated with these disease processes.

Strynadka. High-resolution methods are being used to analyse the detailed structures of enzymes responsible for antibiotic resistance in bacteria.

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