Dr. Nirmala Arul Rayan
Program Manager
Agency for Science, Technology and Research (A*STAR)

Title: An integrative omics approach to understand antidepressant response in rodent brains

Depression is a leading cause of disability worldwide. Selective serotonin-reuptake inhibitors (SSRIs) are the standard of care for depression, and an estimated 350 million individuals worldwide are currently on SSRI treatment. However, remission rates are about 40% and little is known about the mechanism(s) of action of SSRIs due to the lack of systematic, unbiased studies. We undertook a study to unravel the mechanism of action of fluoxetine, the prototypical SSRI, through comprehensive gene expression and epigenome profiling (RNA and ChIP sequencing) of multiple brain tissues in rodents. We identify 2000 potential regulatory elements as fluoxetine induced epigenetic changes and over 1500 genes differentially altered by fluoxetine in a region-specific manner. Using single cell and spatial assays we further highlight the celltype-specific responses. We chart the affected neurotransmitter pathways within and between cell types, and delineate cell populations altered by anti-depressant drugs. In this talk, I will be focusing on how we used 10x Genomics Visium technology to understand the spatial transcriptomic shifts, in specific brain regions in response to fluoxetine.

Speaker Bio:

Dr. Nirmala Arul Rayan is a neurobiologist by training. She is currently the Program Manager for SCISSOR, and her role includes coordinating the research plan across major partner institutions and driving program engagement with industry partners.

Dr. Tom Serge Weber
Postdoc
Walter and Eliza Hall Institute

Title: Probing determinism in epiblast fate using in utero LoxCode barcoding

In simple organisms like C elegans, embryogenesis follows a predetermined path, in which every cell is programmed in exactly the same way producing identical embryos each time. Whether this holds true in more complex organism, for example the mouse or humans is a matter of debate. Here we address this question using LoxCodes, a novel high diversity in utero cellular barcoding technology based on the Cre LoxP system. In our setup, random DNA barcodes are induced in pregnant mice in utero at day E5.5 of development, and a wide range of tissues are interrogated for barcodes a week later at day E12.5 using bulk genomic, single cell and spatial transcriptomics approaches. We find that in mice epiblast fate, while bearing some degree of determinism, seems highly heterogeneous in cellular output, spatial location, and tissue composition.

Speaker Bio:

Tom Weber studied theoretical Physics at Humbold University Berlin (Germany). For his PhD, in the groups of Dr. Michal Or-Guil and Dr. Jorge Carneiro, he develops mathematical models of the cell cycle and the Immune system. He then joins as a Postdoc Prof Ken Duffy's lab in the Applied Math department at the Hamilton Institute in Ireland, to work on theoretical aspects of lineage tracing and leukaemia.

In late 2016 he joins Dr. Shalin Naik's lab at WEHI, with the goal to implement the LoxCode lineage tracing technology. Tom has a track-record in developing new technologies and approaches from concept to implementation and analysis for the biomedical research community. By moving fields, from theoretical Physics, to theoretical Immunology and mathematical Biology, and finally to synthetic, molecular and cell Biology, Tom has acquired a distinctive set of skills and knowledge that he employs to take a truly interdisciplinary approach in his research.