For the brain to function, signals need to pass between neurons in order to control movement, speech, thought, and decision-making. Each individual neuron (there are billions within a single human brain) connects to a vast and complex network of neurons through thousands of synapses. Synapses mediate communication between neurons, affecting how we perceive and react to the world around us—essentially propelling us through life and making us who we are. Dysfunctions in the development or function of synapses are thought to be central to many brain disorders including intellectual disability, schizophrenia, autism, Alzheimer’s disease and addiction.
In Dr. Shernaz Bamji’s lab, researchers are working to understand the molecular mechanisms underlying synapse formation and function to determine why these functions sometimes fail, and whether those same functions can be restored later in life. Recently, the lab has focused on a family of 23 enzymes that mediate a chemical modification called ‘palmitoylation.’
Almost half of all synaptic proteins are can be palmitoylated and nearly one third of all palmitoylating enzymes are mutated in patients with neurodevelopmental and neurodegenerative disease. This not only suggests an important role for these enzymes in the normal functioning of the brain, it also implicates these enzymes in the etiology of a number of brain diseases.
A new CIHR Foundation Grant for Dr. Bamji and her team offers an opportunity to look more closely at how disruptions in palmitoylating enzymes lead to synaptic malfunction and ultimately brain disorders, setting the stage for refined approaches that can be leveraged to develop new therapeutics for restoring brain function and cognition. Dr. Bamji is one of only a few researchers around the world looking at the specific role of palmitoylation in brain disease, and this new funding promises to establish her more firmly as a leader in the field.
“In the long-term, we’d like to determine whether normalizing proper palmitoylation function can ameliorate phenotypes associated with neurological or psychiatric disease in order to uncover potential avenues to treat patients with these disorders,” says Dr. Bamji.
Funded projects led by DMCBH members, students and alumni
CIHR’s Foundation Grant provides long-term support for the pursuit of innovative, high-impact research programs.
- Dr. Shernaz Bamji: Synaptic Plasticity and Dysfunction in the Brain.
- Dr. Helen Tremlett: Disease-modifying Drug Safety and Effectiveness in Multiple Sclerosis [DRUMS].
Project Grants support research projects with a defined endpoint, allowing researchers to pursue innovative, high-risk research questions with potential to improve health outcomes in Canada.
- Dr. Shernaz Bamji: The role of the palmitoylating enzyme, DHHC9, in the formation and function of neuronal connections.
- Dr. Neil Cashman and Dr. Honglin Luo: Role of enteroviral infection in amyotrophic lateral sclerosis.
- Dr. Jeremy Seamans: How is anxiety represented in the anterior cingulate cortex?
- Dr. Wolfram Tetzlaff: Role of endogenous remyelination after spinal cord injury.
- Dr. Blair Leavitt: Development, characterization and treatment of a novel conditional mouse model of pyridoxine-dependent epileptic encephalopathy caused by antiquitin mutations.
Students and alumni
- Congratulations to Dr. Sarah Moore (PI: Dr. Michael Kobor), a current postdoctoral fellow conducting research at the Centre for Molecular Medicine and Therapeutics, for her Banting Postdoctoral Fellowship from CIHR (project title: Prenatal epigenetic programming of infant stress reactivity).
- Congratulations to Samantha Baglot (PI: Dr. Liisa Galea and Dr. Joanne Weinberg), former graduate student who has moved on to a PhD program at the University of Calgary, for her success in receiving a Vanier Scholar Award from CIHR.
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- Congratulations to Dr. Kaarina Kowalec (PI: Dr. Helen Tremlett), former graduate student who has moved on to a postdoctoral fellowship at the Karolinska Institute in Sweden, for her success in receiving a Banting Postdoctoral Fellowship from CIHR.
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