This thesis is in three parts. The first part is a research paper which investigates the ways by which Roscoe Mitchell’s piece, Sound (1965), is a landmark of experimentalism while retaining important influences of the broader jazz tradition. The second part is a piece titled Many Centers for solo drum set, composed and performed in April 2018. The third part is a short album titled Time Studies, recorded in June 2018.

T cells constitute an essential component of the adaptive immune response toimmunogenic antigens both endogenous and exogenous such as those from allergens or viral infections. We present here two studies of T cells, one in which we investigate a non-coding RNA circuit in the control of cytotoxic T cells and one in which we characterize allergen reactive T helper cells in human allergic asthmatic subjects. Proper activation of cytotoxic T cells via the T cell receptor and the costimulatory receptor CD28 is essential for adaptive immunity against viruses and intracellular bacteria. Through biochemical analysis of RNA:protein interactions, we uncovered a novel non-coding RNA circuit regulating cytotoxic T cells composed of the long non-coding RNA (lncRNA) Malat1 (Metastasis Associated Lung Adenocarcinoma Transcript 1) and the microRNA family miR-15/16. miR-15/16 is a widely and highly expressed miRNA family important for cell proliferation and survival. miR-15/16 also play important roles in T cell responses to viral infection, including the regulation of antigen-specific T cell expansion and T cell memory. Comparative Argonaute-2 high throughput sequencing of crosslinking immunoprecipitation (AHC) combined with gene expression profiling in normal and miR-15/16- deficient T cells revealed a network of several hundred direct miR-15/16 targets, many with functional relevance for T cell activation, survival and memory formation. Among these targets, the long non-coding RNA Malat1 contained the largest absolute magnitude miR-15/16- dependent AHC peak in T cells. This binding site was also among the strongest lncRNA:miRNA interactions detected in the T cell transcriptome. We used CRISPR targeting with homology directed repair to generate mice with a 5-nucleotide mutation in the miR-15/16 binding site in Malat1. This mutation interrupted Malat1:miR-15/16 interaction, and enhanced the repression of ixother miR-15/16 target genes, including CD28. Interrupting Malat1 interaction with miR-15/16 decreased cytotoxic T cell activation, including the expression of IL-2 and a broader CD28- responsive gene program. Accordingly, Malat1 mutation diminished memory cell persistence following LCMV Armstrong and Listeria monocytogenes infection. This study marks a significant advance in the study of lncRNAs in the immune system by ascribing cell-intrinsic, sequence- specific in vivo function to Malat1. These findings have implications for T cell-mediated immunity, as well as lung adenocarcinoma and other malignancies where Malat1 is overexpressed. Beyond cytotoxic T cells, T helper cells can differentiate into distinct states marked by stereotypical cytokine expression. In the context of allergic diseases type 2 helper T cells which produce the type 2 cytokines, IL-5, IL-4, and IL-13 can become pathogenic and contribute to a consistently elevated level of type 2 inflammation. In asthma, the lung is the primary site of aberrant inflammation and understanding how this tissue responds to allergens is key. In this study, human subjects were locally exposed to allergen via bronchoscopy. We then assayed the immunological and cellular state of these bronchoscopy samples by multiple high dimensional ‘omic’ technologies: RNAseq, Cytof, and scRNAseq. We then define heterogeneity across these allergic subjects corresponding to type 2 high and type 2 low individuals. In the type 2 high individuals we find that inflammatory monocyte derived populations enter the lung and induce the expression of inflammatory chemokines CCL3, CCL17, and CCL22 likely contributing to increased inflammation in the lung. Further, through scRNAseq we are able to identify Th2 cells recruited specifically by the allergen challenge. In a subset of individuals we could identify TCR clones which were allergen reactive and expanded in the blood post allergen challenge. Indicating that, while these cells are rare in the lung, dampening their function systemically may lead to decreased local inflammation in the lung as well. Understanding all these facets of allergic inflammation in this detailed way is essential for proper clinical understanding of asthma as well as the potential development of novel therapeutic strategies.

The Island of Lost Returns is an intermedia performance and installation work that addresses the social and psychological effects of financial crises as told through the fall of The Buccaneer, a beachside resort on Jekyll Island off the coast of Georgia. The piece has an autobiographical basis, as the motel was in part built and run by my grandfather until his death in 1980, after which my father became increasingly involved with the business. By 2001, the motel company had failed, leaving my father bankrupt.

The piece is comprised of live performance, music, video, and a host of performance objects, sculptures, and paintings. It functions on equal grounds as a performance and as an installation. There is a large hut, which is a replica of The Jekyll Island Club Hotel, originally run by the wealthy business elite of the Gilded Age and site of the creation of the Aldrich Plan, what would later become the Federal Reserve. The hut's presence and fort-like appearance dominate a large portion of the space. It takes on the symbolism of capital gain and power, an imaginary fortress that forms the background of the environment against the tale of the failed family motel.

Eukaryotic flagella (also referred to as cilia) are microtubule-based organelles that protrude from the cell body into the extracellular environment. In addition to powering cell motility and fluid low, flagella mediate the reception of numerous signaling processes that direct developmental programs. Because flagella serve such diverse roles, defects in flagellar morphology produce a pleiotropic array of human diseases.

The assembly and maintenance of flagella relies on intraflagellar transport (IFT), the molecular motor driven traffic of large protein complexes (called trains) carrying flagellar proteins between the cell body and the flagellar tip. To better understand the relationship between flagellar length and IFT, we developed a method to quantify IFT in the flagella of Chlamydomonas reinhardtii using total internal reflection fluorescence microscopy (TIRF, described in detail in chapter 2). In chapter 1, we measured changes in anterograde (base to tip) IFT during flagellar regeneration and found that IFT train size is inversely proportional to flagellar length, and may thus determine the steady state length of flagella. In chapter 3, we performed a pharmacological screen for impaired cell motility in Chlamydomonas and identified a small molecule that reduces flagellar length in several organisms, while affecting both IFT and actin dynamics. In chapter 4, we performed a genetic screen for impaired Chlamydomonas cell motility and isolated a temperature-sensitive mutant in the heavy chain of IFT dynein, the retrograde motor that returns IFT trains from the flagellar tip to the cell body. Unlike mutations in the anterograde kinesin motor, which impede both flagellar assembly and maintenance, the dynein mutant (named dhc1b-3) experiences defects in assembly but not maintenance despite significant reductions in both dynein protein and IFT activity. This surprising observation has forced us to rethink the relationship between IFT and the control of flagellar length.