The C. elegans ALA neuron : its transcriptome and role in inducing sleep

A long-standing yet to be accomplished task in understanding behavior is to dissect the function of each gene involved in the development and function of a neuron. The C. elegans ALA neuron was chosen in this study for its known function in sleep, an ancient but less understood animal behavior. Single-cell transcriptome profiling identified 8,133 protein-coding genes in the ALA neuron, of which 57 are neuropeptide-coding genes. The most enriched genes are also neuropeptides. In combination with gain-of-function and loss-of-function assays, here I showed that the ALA-enriched FMRFamide neuropeptides, FLP-7, FLP-13, and FLP-24, are sufficient and necessary for inducing C. elegans sleep. These neuropeptides act as neuromodulators through GPCRs, NPR-7, and NPR-22. Further investigation in zebrafish indicates that FMRFamide neuropeptides are sleep-promoting molecules in animals. To correlate the behavioral outputs with genomic context, I constructed a gene regulatory network of the relevant genes controlling C. elegans sleep behavior through EGFR signaling in the ALA neuron. First, I identified an ALA cell-specific motif to conduct a genome-wide search for possible ALA-expressed genes. I then filtered out non ALA-expressed genes by comparing the motif-search genes with ALA transcriptomes from single-cell profiling. In corroborating with ChIP-seq data from modENCODE, I sorted out direct interaction of ALA-expressed transcription factors and differentiation genes in the EGFR sleep regulation pathway. This approach provides a network reference for the molecular regulation of C. elegans sleep behavior, and serves as an entry point for the understanding of functional genomics in animal behaviors.

Cryogenic Silicon Optical Reference Cavities

Thermodynamical fluctuations in temperature and position exist in every physical system, and show up as a fundamental noise limit whenever we choose to measure some quantity in a laboratory environment. Thermodynamical fluctuations in the position of the atoms in the dielectric coatings on the mirrors for optical cavities at the forefront of precision metrology (e.g., LIGO, the cavities which probe atomic transitions to define the second) are a current limiting noise source for these experiments, and anything which involves locking a laser to an optical cavity. These thermodynamic noise sources scale physical geometry of experiment, material properties (such as mechanical loss in our dielectric coatings), and temperature. The temperature scaling provides a natural motivation to move to lower temperatures, with a potential huge benefit for redesigning a room temperature experiment which is limited by thermal noise for cryogenic operation.

We design, build, and characterize a pair of linear Fabry-Perot cavities to explore limitations to ultra low noise laser stabilization experiments at cryogenic temperatures. We use silicon as the primary material for the cavity and mirrors, due to a zero crossing in its linear coefficient of thermal expansion (CTE) at 123 K, and other desirable material properties. We use silica tantala coatings, which are currently the best for making high finesse low noise cavities at room temperature. The material properties of these coating materials (which set the thermal noise levels) are relatively unknown at cryogenic temperatures, which motivates us to study them at these temperatures. We were not able to measure any thermal noise source with our experiment due to excess noise. In this work we analyze the design and performance of the cavities, and recommend a design shift from mid length cavities to short cavities in order to facilitate a direct measurement of cryogenic coating noise.

In addition, we measure the cavities (frequency dependent) photo-thermal response. This can help characterize thermooptic noise in the coatings, which is poorly understood at cryogenic temperatures. We also explore the feasibility of using the cavity to do macroscopic quantum optomechanics such as ground state cooling.