Combinatorial effects of Alpha- and Gamma-Protocadherins on neuronal survival and dendritic self-avoidance

The clustered Protocadherins (Pcdhs) comprise 58 cadherin-related proteins encoded by three tandemly-arrayed gene clusters, Pcdh-alpha, -beta, and --gamma (Pcdha, Pcdhb, Pcdhg). Pcdh isoforms from different clusters are combinatorially expressed in neurons. They form multimers that interact homophilically, and mediate a variety of developmental processes, including neuronal survival, synaptic maintenance, axonal tiling and dendritic self-avoidance. Most studies have analyzed clusters individually. Here, we assess functional interactions between Pcdha and Pcdhg clusters. To circumvent neonatal lethality associated with deletion of Pcdhgs, we used Crispr-Cas9 genome editing in mice to combine a constitutive Pcdha mutant allele with a conditional Pcdhg allele. We analyzed roles of Pcdhas and Pcdhgs in the retina and cerebellum from mice (both sexes) lacking one or both clusters. In retina, Pcdhgs are essential for survival of inner retinal neurons and dendrite self-avoidance of starburst amacrine cells, while Pcdhas are dispensable for both processes. Deletion of both Pcdha and Pcdhg clusters led to far more dramatic defects in survival and self-avoidance than Pcdhg deletion alone. Comparisons of an allelic series of mutants support the conclusion that Pcdhas and Pcdhgs function together in a dose-dependent and cell-type specific manner to provide a critical threshold of Pcdh activity. In the cerebellum, Pcdhas and Pcdhgs also act synergistically to mediate self-avoidance of Purkinje cell dendrites, with modest but significant defects in either single mutant and dramatic defects in the double mutant. Together, our results demonstrate complex patterns of redundancy between Pcdh clusters and the importance of Pcdh cluster diversity in postnatal CNS development

Observations of Exoplanet Atmospheres

The focus of this thesis is the observation of extrasolar planet atmospheres. Our research utilizes a variety of telescopes and analysis techniques to observe planets with a variety of properties. In Chapter 1, we present a brief overview of the current state of exoplanet detections. In Chapter 2 is a comprehensive analysis of hot-Jupiter phase curves observed by the Kepler Space Telescope, where planetary properties including albedo, temperature, radius and mass are reported. In Chapter 3, a larger sample of Kepler phase curves are analyzed, including that of an ultra-short period rocky planet. Unlike in Chapter 2, the analysis of this sample also includes a measurement of the phase curve peak brightness offset, which it then used to infer brightness variations across the planet's surface. In Chapter 4, high-resolution Doppler spectroscopy is used to search for water absorption in the transmission spectrum of 55 Cancri e and in Chapter 5 ground-based differential spectrophotometry is used to search for the water absorption signature of HD189733 b in transit observations at K and H band wavelengths. In the final Chapter, future exoplanet discovery missions, and follow-up observing instruments, are described and predictions are made about the success of future exoplanet atmospheric studies.Ph.D