Dr. Christopher Brett and his research team at Concordia University study the molecular basis of lysosome physiology
and are translating knowledge to develop new exosome-based therapies.
Lysosomes are the recycling compartments of all eukaryotic cells, including the trillions of cells that make up you. Our team is dedicated to understanding how lysosomes function and promote longevity.
Exosomes mediate intercellular communication underlying diverse physiology. Our team is re-engineering them to develop new biological therapies.
© Concordia University, photo by Lisa Graves
Our laboratory uses a unique combination of
genetics, biochemistry and advanced microscopy
to understand the molecular mechanisms underlying fundamental lysosome biology, primarily using baker's yeast (S. cerevisiae) and its vacuolar lysosome as models.
Our claim to fame is the discovery of the IntraLumenal Fragment (ILF) pathway, a genuinely new cellular protein degradation process that selectively down-regulates lysosomal nutrient transporters. When two lysosomes fuse, they first dock together with the underlying fusion machinery assembling into a ring. Unneeded or damaged transporter proteins embedded their membranes are selectively sorted into the encircled area, called the boundary membrane. Upon lipid bilayer merger (fusion), apposing boundaries merge and form a protein-laden ILF entrapped within the lumen of the fusion product (a single large lysosome) where it is exposed to acid hydrolyses and degraded.
We are now focused on understanding how this ILF pathway contributes to maintenance of organelle identity and integrity, to remodeling protein and lipid landscapes observed during cell aging programs, and to total cell proteostasis and metabolism.
McNally et al. (2017) Developmental Cell 40:147-61.
With unique expertise in intralumenal vesicle (ILV) and intralumenal fragment (ILF) biogenesis,
we have initiated a second project in the laboratory that uses approaches in synthetic biology
to engineer humanized yeast extracellular vesicles as next-gen biologic therapies.
Both ILVs and ILFs can be released as exosomes or extracellular vesicles by eukaryotic cells to mediate intercellular communication underlying diverse physiology. We aim to realize their incredible therapeutic potential by re-engineering them using S. cerevisiae as a platform, as it offers many advantages from its unmatched genetic toolkit to easy upscaling for bioproduction.
Our research relies on collaborations and resources within the:
JOIN THE BRETT LAB!
We are recruiting talented graduate (PhD, MSc) and undergraduate (Honors thesis, USRA, MITACS) students to join our team in Montreal, Canada studying lysosome biology and humanized yeast exosomes for therapeutic applications. Please send a (1) CV, (2) copy of your transcript, and (3) letter of interest to:
Or apply to the NSERC SynBioApps Training Program
GET IN ToUCH!
Christopher L. Brett, Ph.D.
7141 Sherbrooke St. W.
Montréal, QC Canada H4B 1R6
SP-553.15 (office) SP-534 (lab)
Tel: +1 514 848-2424 x3398