Thomas Klarić

Biography

Dr. Thomas Klarić seeks to combine his interests in neuroscience and glycobiology to address questions of fundamental importance at the interface of these two fields. He graduated from the University of Adelaide with a Bachelor of Biotechnology (Honours) in 2005 and obtained a PhD from the School of Molecular and Biomedical Science at the same institution in 2012. Between 2012 and 2014 he was employed as a postdoctoral researcher in the University of Adelaide Stroke Research Programme where he used rodent models of stroke to investigate the effectiveness of stem cell therapy as a treatment option. In 2014 he was awarded a NewFelPro postdoctoral fellowship as part of the FP7 Marie Skłodowska-Curie Actions initiative to work in Genos Ltd. on the Human Neuroglycome Project where he investigated the spatiotemporal profile of N-glycosylation in the human brain using liquid chromatography and mass spectrometry. In 2018 he received a Fulbright fellowship to undertake postdoctoral training at the Yale University School of Medicine where his research focused on transcriptional control of mouse neurodevelopment. As of April 2020, he is once again in Genos Ltd. where he is applying his expertise in glycan analysis to investigate key research questions at the cutting edge of neuroglycobiology.

Description of the general focus of the symposium "Glycobiology of the Brain"

Glycoconjugates play an essential role in many fundamental neurobiological processes occurring at the cell membrane. In the brain, these glycoconjugates have a role in tissue patterning and neural development by modulating neural cell behavior, synaptic formation, and acting on neuronal network function and remodeling. It is therefore clear that a deeper understanding of carbohydrates and their functions in the central nervous system biology is of utmost importance in advancing the field of neuroscience. Despite the undeniable importance of the carbohydrates in neurobiology, however, glycans are rarely under the spotlight in neuroscientists’ meetings thus making this type of session novel and unique. In this symposium we intend to present the latest advances in the field to a broad audience of neuroscientists with the aim of highlighting the increased cross-disciplinary collaboration between (glyco)biologists and the neuroscientists’ community. The session explores the structural and functional roles of the various forms of carbohydrates in the physiology and pathology of the nervous system. The talks will focus on the evolution of the mammalian brain from the comparative N-glycomics point of view and on the changes of brain sialylation in healthy brain development and in neuropathologies thus presenting the state-of-the-art techniques enabling the scientists to tackle the multidisciplinary aspects of the glycobiology of the brain. The first part of the symposium will be focused on the new findings on both the spatial organization of the brain N-glycome as well as its evolutionary trajectory in mammals from a multiregional comparison of brain N-glycosylation in various species. The second part of the symposium will tackle the changes of metabolic sialylation and desialylation in the developing and mature murine and human brain with a special focus on sialic acid distribution and function in human neuropathologies such as epilepsy and glioblastoma. 

Talk: "Insights into the evolution of the mammalian brain via comparative N-glycomics"

Numerous comparative “omics” studies have revealed unique aspects of human neurobiology, yet an evolutionary perspective of protein glycosylation in the mammalian brain is lacking. Asparagine-linked glycosylation (N-glycosylation) is a post-translational modification that is a common feature of transmembrane, secreted, and extracellular proteins and it is critically involved in many aspects of neurobiology. To gain an insight into the evolutionary trajectory of N-glycosylation in the mammalian brain, we comprehensively characterised rat, macaque, chimpanzee, and human N-glycomes from four brain regions using chromatography combined with mass spectrometry, then integrated these data with complementary glycotranscriptomic data. We found that in primates the brain N-glycome has diverged more rapidly than the underlying transcriptomic framework, providing a means for rapidly generating additional inter species diversity. We uncovered numerous phylogenetic trends in brain protein N-glycosylation as well as several human-specific adaptations. Taken together, our data suggest that brain N-glycome evolution in hominids has been characterized by an overall increase in complexity coupled with a shift in sialic acid linkage.