Genomics has undergone a resolution revolution, such that the nucleic acid content of individual cells are now sequenced routinely in high-throughput mode. Thus we can define the cellular composition of tissues in an unbiased and comprehensive way using single cell transcriptomics, revealing the molecular fingerprint of cell states and their predicted signalling circuits in tissues across development and disease. I will illustrate this with the human healthy and asthmatic lung, as well as the maternal-fetal interface in the first trimester placenta/decidua

Abstract:
Our lives are intimately tied to Earth’s 24-hour solar cycle through genetically encoded clocks that coordinate our physiology and behavior with environmental light/dark cycles. Disruption of circadian rhythms through shift work or jet lag can lead to metabolic disorders, cardiovascular disease, and cancer. Our lab studies how molecular clocks measure time on a daily basis to better understand how they use this information to coordinate and control our biology. I’ll speak about some recent advances from our lab using polymorphisms that give rise to morning lark and night owl behavior in people to shed light on the biochemical mechanisms of our molecular clock. Our long-term goal is to leverage a mechanistic understanding of clock function to develop therapeutic strategies that exploit circadian rhythms to improve human health and wellbeing.

Abstract:

Synapses are the electrical switches of the brain, underpinning much of the signaling between neurons and directly involved in nearly all aspects of innate and learned behaviors. The key signaling machinery – neurotransmitter receptors and transporters – are also implicated in a large number of neurological diseases or disorders and are the targets of multiple therapeutic agents and illicit substances. Synapses are sites of three choreographed processes – calcium-dependent release of neurotransmitter into extracellular spaces, detection of neurotransmitter by ion channels, and removal of neurotransmitter by transporters. In my talk I will focus on the last two activities.

On the one hand, binding of the released neurotransmitters to transmitter-gated ion channels initiates local changes in membrane potential and these changes, when summed, initiate action potentials that are propagated throughout neuronal circuits. On the other hand, the ion channels also allow for calcium entry into cells, thus initiating chemical signaling via calcium-dependent pathways. Quenching of the neurotransmitter within the synapse and surrounding spaces is accomplished by membrane-bound transporters, molecular machines that harness pre-existing ion gradients to ‘pump’ transmitter into cells, thereby enabling subsequent cycles of neurotransmitter signaling.

Here, I illuminate how neurotransmitters transduce binding events into the opening of ion channel-coupled receptors, and on the fascinating mechanisms by which neurotransmitter transporters take-up transmitter from the synaptic cleft and are modulated by clinically relevant drugs.