The Weaver Lab
We are a multidisciplinary drug discovery lab; our principle aim is to find a disease-modifying (or curative) treatment for Alzheimer's Disease and Dementia. The process of finding a safe and effective drug is long, and requires the tandem work of multiple scientific teams.
In the first step towards drug discovery, our biologists explore the pathological processes of Alzheimer's disease to probe for druggable targets. These projects involve meticulous analysis of the behavior of brain cells, and their components, both in their normal and disease states. Our biologists, in collaboration with partners in other labs and industry, work to isolate the specific proteins and molecules that lead to the degeneration of brain cells, and from there, how we can stop these elements from malfunctioning.
Our theoretical chemists explore the chemical basis for the origin of Alzheimer's disease, or how pathologies interact with normal biological systems on an atomic level. Their work takes them to the cutting edge of atomic modeling, and typically involves assimilating the quantum mechanical behavior particles with complexities of biological systems. A substantial contribution made by our theoretical chemists was isolating the precise process by which misfolded proteins in Alzheimer's disease (amyloid beta) can eventually form pores or holes in the membranes of neurons.
Once a target has been identified and validated, our team of computational chemists then begins to investigate how we can intervene to prevent these elements from becoming diseased. Typically, a process of drug design involves developing a molecule that will prevent two elements of a pathological system from interacting. For example, our computational team may devise molecules that stop two proteins from interacting with each other, or blocking the active-site of a hazardous enzyme. Our computational chemists also screen millions of compounds in silico (virtually) and thus can help direct our lab to making the best choices for further investigation.
Returning to the wet lab, our team of synthetic organic chemists make the molecules that we believe have the best chance of success. Depending on the nature of the molecule under investigation, the synthesis can require multiple intermediates, each with their own purification and characterization steps. On occasion, our chemists have devised novel synthetic procedures which have been published in their own right.
Protein and Cellular Biology
Upon successful synthesis and purification of novel drug molecules, protein and cellular - also known as in vitro - biologists take over , and test the molecule within biological systems to identify its efficacy. These may involve relatively simple protein assays which can be completed over 8 to 10 hours or extensive cellular assays which involve incubation over weeks and days. The results of these assays then help redirect the computational and synthetic chemistry in an iterative process where molecules are made, tested, refined, remade and retested until a viable clinical candidate is discovered.
The most promising drug candidates are then put through a battery of pharmacological testing in which the drug is first exposed to multi-cellular living systems. These assays give information not only about efficacy, but the safety, absorption, distribution, metabolism, and excretion of the potential drug. At this stage, drugs are also tested for their ability to cross the blood brain barrier and effectuate targets within the brain. The most successful of these drugs will go on to early trials in humans and onwards.
The lab is home to a variety of scientists, from various disciplines, including:
- Research Associates
The lab is also home to trainees at various levels of their academic careers, namely:
- Post-Doctoral Fellows
- Graduate Students
- Medical Students
- Undergraduate Students
- Volunteer Summer Students
Our lab at the Krembil Research Institute includes full service organic chemistry, biological and computational facilities. We also have our NMR (Nuclear Magnetic Resonance), Mass Spectroscopy, Cell Culture and Pharmacology programs.