research
Our current program is completely focused on Huntington's disease using four principle areas of research technology
and approaches:
Cell Biology:
Our lab has pioneered many live cell imaging techniques and designed microscopes that interface with
sophisticated computer programs that allow precise quantitative measure of observation of living cells as they die from
toxic activity of the huntingtin protein. These techniques are critical to understanding Huntington's disease at the single
cell level, as biochemistry of this protein is technically difficult due to its unusually large size, almost 7X larger than
typical human proteins. This work is done within our own lab’s custom microscopy and computing suite, and within the
McMaster Biophotonics facility which we helped establish in 2005. This is a state-of-the-art, $20M facility that uses the
biophysical principles of light to understand protein activity, protein movement, and disease mechanisms. This facility
gives Dr. Truant all the tools of large corporate pharmaceutical research, and local expertise with the McMaster
Engineering, Chemistry and Physics departments.
Proteomics and Biochemistry:
The methods define new interacting proteins with huntingtin in order to understand the exact mechanism of
Huntington's disease. These biochemical techniques use protein affinity chromatography as a method to purify new
huntingtin interactors, which are then identified by a highly sensitive technique of mass spectrometry. Using these
methods, literally billionths of a gram of protein can be accurately identified. Understanding interactor with huntingtin is
the basic scaffold of knowledge to define and develop new drug targets for HD.
Chemical biology:
Chemical biology refers to the use of small bioactive molecules (which may be precursors to drugs) as tools to
understand the cell biology of the Huntingtin protein. These methods include massive scale high throughput screening
(HTS) and high content screening (HCS) screening assays on thousands of chemical compounds by the use of robotics.
McMaster is an innovator in this area, with one of the first HTS facilities in Canada, and one of the first, and strongest
Chemical Biology training programs in the world.