The nano-meter scale organization and function of phosphoinositide signaling at central synapses

2014 Seed Grant
Xuelin Lou
Department of Neuroscience
University of Wisconsin

1) Lipid signaling plays an essential role in synaptic transmission and aberrant lipids signaling has been implicated in many brain diseases including AD, Down’s syndrome and epilepsy; however, we know very little about how lipids works at nanometer scales in the plasma membrane of neurons. We propose to develop and apply innovated super-resolution optical imaging to map the molecular topography of these key signaling molecules (PI(4,5)P2 and syntaxin1A) at nerve terminal membrane at nanometer precision. The proposed research will have a profound impact on synaptic biology and neuron communication. It will also have broad medical relevance beyond the cell biology of neurons, and help to develop better therapeutic rationales for a few complex brain diseases mentioned above.

2) We will establish a novel super-resolution optical imaging approach for lipid signaling study at nanometer precision, which improves the spatial resolution of imaging ~10 times compared with other modern light microscopy including confocal, two-photon or TIRF microscopy. This will open a new avenue toward cellular and molecular neuroscience. The novel approaches to acute manipulate local PIs in the PM of live cells may have broader application in the other relevant fields of lipid signaling. Preliminary data generated from this study will be critical for a successful federal project (RO1 or NSF).

Other Grants

Sarah C. Goetz, Ph.D., Duke University
Uncovering a Novel Role for Primary Cilia in Eph/Ephrin Signaling in Neurons
2022 Seed GrantSarah C. Goetz, Ph.D. Duke University Women’s Council Seed Grant Primary cilia are tiny projections from cells that function like an antenna- they receive and may also send…
Erin M. Gibson, Ph.D., Stanford University
Circadian Regulation of Oligodendroglial Senescence and Metabolomics in Aging
2022 Seed GrantErin M. Gibson, Ph.D.Stanford University The brain consists of two main classes of cells, neurons and glia. Glia make-up more than half of the cells in the brain…
Yvette Fisher, Ph.D., University of California, Berkeley
Dynamic Modulation of Synaptic Plasticity During Spatial Exploration
2022 Seed GrantYvette Fisher, Ph.D.University of California, Berkeley The Virginia (Ginny) & Roger Carlson Seed Grant Cognitive flexibility is critical for appropriately adjusting thoughts and behaviors to meet changing demands…
Byoung Il Bae, Ph.D., University of Connecticut
Unique Vulnerability of Developing Human Cerebral Cortex to Loss of Centrosomal Protein
2022 Seed GrantByoung Il Bae, Ph.D.University of Connecticut Carl & Marilynn Thoma Foundation Seed Grant The cerebral cortex is the largest and outermost part of the human brain. It is…