11:19am Wednesday 11 December 2019

U of T researcher has lipids on his mind

U of T professor Anurag Tandon is training a new generation of researchers to look at the role lipids play in Parkinson’s and Alzheimer’s disease thanks to a six-year $1.8M Canadian Institutes of Health Research (CIHR) Strategic Training Initiative in Health Research in Neurodegenerative Lipidomics.

Despite past and current advances in neurodegenerative disease research, it is not known why some cells (and some people) are uniquely susceptible to Alzheimer and Parkinson’s diseases. Part of this mystery may lie in the composition of their brain “fat” (i.e., lipids). Lipids are the building blocks of biological membranes and make up half the weight of brain tissue. But not all lipids are the same. Different lipids display unique properties that affect how a cell will respond to proteins linked to disease pathology.

With new CIHR funding, Tandon, a professor of medicine affiliated with U of T’s Tanz Centre for Research in Neurodegenerative Diseases, and his 17 other collaborators seek to provide young scientists with a new understanding of how this “fat” impacts protein function in neurodegenerative disease to render some cells (and people) susceptible to these devastating diseases and others resistant.

“We are now finding interactions between protein and lipids, which we always knew existed but were overlooked due to the technological challenges associated with identifying these lipids in disease brain. Thanks to CIHR’s Strategic Training Initiative in Health Research in Neurodegenerative Lipidomics, we can now pursue these interactions further as they are part and parcel of the neurodegenerative process,” explained Tandon. “For example, we’ve identified a particular lipid that interacts with one of the key factors involved in Parkinson’s pathology, α-synuclein. We are pursuing this interaction to see whether it is involved in the protein aggregation that occurs in diseased brain.”

This finding was first published in BMC Neuroscience but now, with new CIHR funding, Dr Tandon’s trainees will be able to accelerate their collaborative work with graduate students and post-doctoral fellows in laboratories of Drs. Daniel Figeys and Steffany Bennett at the University of Ottawa to use the emerging power of mass spectrometry to identify more of these lipids and determine impact on disease.

This unique trans-institutional training program is a collaborative initiative between the University of Ottawa, Carleton University, University of Toronto, Sunnybrook Health Sciences Centreand Ottawa Hospital Research Institute (OHRI) led by Dr Steffany Bennett (uOttawa). The program applies a targeted systems approach to integrative research that promotes and facilitates cross-disciplinary training and knowledge exchange in order to advance critical research in neurodegenerative lipidomics. The team focuses on training highly qualified students and early-career professionals to apply lipidomic technologies and strategies to identify and reverse pathogenic changes in lipid metabolism that render neurons vulnerable to Alzheimer’s Disease (AD), Parkinson’s Disease (PD), depression and stroke.

“Lipidomics uses the power of mass spectrometry, the depth of lipid biochemistry, the insight of neuronal cell biology, and, unique to our team, the communication afforded by hybrid visualization technologies to define the crucial role that brain lipids play in neurodegenerative disease and the demonstrate the impact of intervention,” explained Bennett.

“From the perspective of disease pathology and the clinical perspective for the individual, our trainees will learn a new understanding of disease pathology and will be able explore new strategies to correct these pathologies,” said Tandon.

The training program supports its curriculum through its extended mentorship network of principal investigators and peer-mentors, as well as through award funding to undergraduates, graduate students, and post-doctoral fellows. In addition to hands-on research, trainees are encouraged to reach-out and participate in the larger scientific research community through the program’s support of authoring of joint publications, presenting work at conferences, and travelling to perform research in the field or with host labs around the world. The program also recognizes the challenges of collaborating across disciplines and supports the development of new integrative ways to connect and communicate.

Faculty team members include Professor Paul Fraser of medical biophysics and the Tanz Centre for Research in Neurodegenerative Diseases (CRND), University of Toronto and Professors Lanctôt of psychiatry and Sandra Black of medicine, both based at Sunnybrook Health Science Centre, Toronto.

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