Circadian clocks enable organisms to anticipate predictable environmental changes over 24-hour day-night cycles on Earth to promote health and fitness. Since the discovery of the first clock gene in Drosophila melanogaster, Drosophila has been a model organism revealing the molecular underpinnings of animal circadian clocks. The first two chapters of this thesis will investigate the regulation of molecular clocks by posttranslational mechanisms. In particular, we will investigate the functions of core clock protein phosphorylation in Drosophila. Despite the importance of rhythmic gene expression programs produced by the molecular clock in generating daily biological rhythms, it has now been established that phosphorylation of core clock proteins that make up the molecular clock represent central and conserved timing mechanisms across organisms. Chapter One will investigate mechanisms by which phosphorylation regulates the major circadian transcriptional activator CLOCK (CLK) of rhythmic genes in D. melanogaster. CLK phosphorylation states exhibit daily rhythms and regulate its abundance, subcellular localization, and transcriptional activity. We characterized the role of casein kinase 1 alpha (CK1a) as a novel CLK kinase. We identified CK1a-dependent CLK phosphorylation sites using mass spectrometry proteomics. We next characterized the function of phosphorylation at Serine 13 (S13) residue. Our results showed that CLK(S13) phosphorylation reduces the binding activity of CLK to circadian promoters, therefore reducing CLK transcriptional activity. We also showed that CK1a-CLK interaction is dependent on PERIOD (PER), the circadian transcriptional repressor that is known to inhibit CLK function. We revealed a mechanism by which repressor-dependent phosphorylation of an activator inhibits its transcriptional activity and thus closing the transcriptional-translational feedback loop (TTFL) of the molecular clock. In Chapter Two, we focused on a comprehensive investigation of phosphorylation on TIMELESS (TIM), the heterodimeric partner of PER. We first identified phosphorylation sites on PER-bound TIM using mass spectrometry. We found that abolishing phosphorylation at some of these residues caused altered circadian behavioral rhythms. Phosphorylation at Serine 1404 (S1404) residue promotes TIM nuclear accumulation by reducing its interaction with exportin 1 (XPO1), a nuclear export machinery. Reduced nuclear localization of TIM in S1404A nonphosphorylatable fly mutants not only resulted in lower level of nuclear PER and TIM, but also showed dampened daily rhythms in CLK phosphorylation. This is likely caused by reduced recruitment of CLK kinase by PER-TIM complex. Taking Chapter One and Two together, we provide mechanistic insights into CLK and TIM phosphorylation and how these posttranslational modifications are indispensable for the maintenance of 24-hour molecular oscillation to regulate circadian rhythms. Chapter Three will review our current understanding of the function of Drosophila TIM (dTIM) and mammalian TIM (mTIM). dTIM is a cardinal clock protein, whereas the role of mTIM in regulating circadian rhythms are under debate since it was first identified over two decades ago. We will summarize the circadian and non-circadian roles of the two TIM paralogs and discuss the potential mechanisms by which mTIM regulates circadian rhythms via its non-circadian roles. We will conclude Chapter Three by summarizing recent findings about potential functional parallel between mTIM and dTIM. Overall, the research included in this thesis will provide mechanistic insights into the regulation of animal circadian clocks and contribute to future development of therapeutics for clock-related human diseases including cancer.

This dissertation aims to employ density functional theory calculations to investigate energy conversion materials. The main focus of this dissertation is on the emerging photovoltaic materials halide perovskites: the third and fourth chapters discuss perovskite-derived halides A2BX6 and double perovskite halides A2MM'X6, respectively. The fifth chapter discusses a novel material for photocatalytic water splitting.

In Chapter 3, we focus on a perovksite-derived halide A2BX6 for photovoltaic applications. The electronic structure and energetic stability of A2BX6 halide compounds with the cubic and tetragonal variants of the perovskite-derived K2PtCl6 prototype structure are

investigated computationally within the frameworks of density-functional-theory and hybrid functionals(HSE06). The HSE06 calculations are undertaken for seven known A2BX6 compounds with A = K, Rb and Cs, and B = Sn, Pd, Pt, Te, and X = I. Trends in band gaps and energetic stability are identified, which are explored further employing semi-local density-functional-theory(DFT) calculations over a larger range of chemistries, characterized by A = K, Rb, Cs, B = Si, Ge, Sn, Pb, Ni, Pd, Pt, Se and Te and X = Cl, Br, I. For the systems investigated in this work, the band gap increases from iodide to bromide to chloride. Further, variations in the A site cation influences the band gap as well as the preferred degree of tetragonal distortion. Smaller A site cations such as K and Rb favor tetragonal structural

distortions, resulting in a slightly larger band gap. For variations in the B site in the (Ni, Pd, Pt) group and the (Se, Te) group, the band gap increases with increasing cation size. However, no observed chemical trend with respect to cation size for band gap was found for

the (Si, Sn, Ge, Pb) group. The findings in this work provide guidelines for the design of halide A2BX6 compounds for potential photovoltaic applications.

In Chapter 4, we focus on building a database for the double perovskite halides and employ the database to identify new materials for photovoltaic applications. Starting from a consideration of the octahedral and tolerance factors of ~2000 candidate double-perovskite

compounds, we compute structural, electronic and transport properties of ~1000 using first-principles calculations based on DFT methods. The computational results have been assembled in a database that is accessible through the Materials Project online. As one potential application, double perovskites are candidates in the search for lead-free halide photovoltaic absorbers. We present the application of our database to aid the discovery of new double perovskite halide photovoltaic materials, by combining the results with optical absorption and phonon stability calculations. Eleven compounds from three distinct classes of chemistries were identified as promising solar absorbers and the complex chemical trends for band gap within each of these are analyzed, to provide guidelines for the use of substitutional alloying as a means of further tuning the electronic structure.

In Chapter 5, we focus on the SrNbO3+d structures with different oxygen compositions and discuss their electronic properties based on DFT calculations of their electronic structures and charge density distributions. Under low oxygen pressure, films formed have the SrNbO3 perovskite structure. SrNbO3 has a heavily degenerate conduction band and a high carrier density. When growing under higher oxygen pressure, the carrier density decreases and the films become more insulating. The excess oxygen leads to the formation of extra

oxygen planes with a density that increases with d; at the nominal composition SrNbO3.4, these extra oxygen planes should appear every 5 unit cells. According to our calculation for SrNbO3.4, valence electrons are confined in the middle of two neighboring extra oxygen planes. These characteristics of the electronic structure lead to strong conventional plasmonic effects and strongly correlated plasmonic effects for SrNbO3 and SrNbO3.4, respectively.