Browsing Genetics by Title
Now showing items 56-75 of 146
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High throughput determination of sequence-function relationships in protein and RNA
As more individuals have their genomes sequenced, more genetic variation is discovered. The problem of interpretation of this variation has become intractable using established methods of linking phenotype to genotype, ... -
High-throughput functional characterization of cancer specific alternative polyadenylation
RNA dysregulation is a ubiquitous feature of human cancers and misexpression of even a single RNA isoform is sufficient to drive cancer. Among types of RNA processing, alternative cleavage and polyadenylation (APA), a ... -
High-throughput interrogation of genome function and cellular lineage
Mutations can reveal how biological functions are encoded in our DNA, and how biological specimens relate to one another. In nature, mutations occur infrequently and are subject to natural selection. Therefore, to better ... -
High-throughput methods of studying human cytochrome P450 activity in Saccharomyces cerevisiae
Genetic variation in cytochrome P450 enzymes leads to inter-individual variability in drug metabolism, while lack of functional annotation prevents most variants from being used to inform drug choice and dosing. To measure ... -
High-throughput methods to analyze protein-DNA and protein-RNA interactions
The genome of a cell contains the information to make thousands of RNA and protein molecules. However, a cell typically expresses only a fraction of its genes, with different phenotypes arising because of differentially ... -
Human-specific duplicate genes: new frontiers for disease and evolution
Gene duplication is a fundamental force contributing to the evolution of novel traits, genomic diversity among species and individuals, and disease. In this dissertation, I characterize the evolutionary history, diversity, ... -
Identification and characterization of genes that modify tubulogenesis defects caused by over-expression of Imaginal Disc Growth Factor-3 using the Drosophila dorsal appendage model, a partial genomic expedition
Biological tube formation underlies organ development, and when disrupted, can cause severe birth defects. To investigate the genetic basis of tubulogenesis, I study the formation of Drosophila melanogaster eggshell ... -
Identification of candidate substrates of the leucine rich repeat kinase 2 by mass spectrometry-based phosphoproteomics
Mutations in the kinase domain of the leucine rich repeat kinase (LRRK2) have been implicated in heritable forms of Parkinson’s disease (PD). Specifically, a glycine to serine mutation (G2019S) has demonstrated hyperactive ... -
Identifying Neural Pathways of Stress and Fear with Retrograde Viral Tracing and Single Cell RNA Sequencing
The brain is made up of millions of neurons, often making thousands of connections each. Interrogating individual neurons activated by stressors is the equivalent of finding a needle in a haystack. Here we describe ... -
Identifying New Genes for Inherited Breast Cancer by Exome Sequencing
(2014-02-24)Breast cancer is the most common cancer among American women and family history is an important risk factor for its occurrence. More than 20 genes have been identified with inherited mutations that lead to significantly ... -
Immune consequences and therapeutic targeting of disrupted RNA splicing in cancer
Immunotherapies, such as checkpoint blockade, CAR-T cells, and vaccines, have proven to be a valuable tool to treat various types of cancer. This class of therapy capitalizes on the immune system’s natural ability to ... -
Improving peptide detection in mass spectrometry-based proteomics
Over the last 30 years, the field of computational mass spectrometry-based proteomics has made great strides. Specifically, the development of database search engines has allowed for the automatic annotation of observed ... -
Inferring whole-genome 3D chromatin structures from diploid Hi-C data
The three-dimensional organization of the genome plays an important part in regulating numerous basic cellular functions, including gene regulation, differentiation, the cell cycle, DNA replication, and DNA repair. Assays ... -
Insights into mechanisms of Pseudomonas aeruginosa virulence: cyanide as a weapon and the complexity of its regulation
(2001)This dissertation presents investigations into virulence mechanisms and virulence-gene regulatory circuitry in the bacterium Pseudomonas aeruginosa . P. aeruginosa is a medically important human pathogen that causes serious ... -
Interpreting variation in pharmacogenes using multiplex assays
With the advent of genome sequencing technologies, our ability to read DNA sequences is unprecedented. However, understanding how the variation we encounter impacts humans is a formidable challenge. Technologies like ... -
Investigating the duplication and evolution of essential fertilization proteins
Duplication processes such as whole gene duplication and tandem domain expansion are important for the evolution and functional diversification of essential protein families. While whole gene duplications are well established ... -
Learning from Large-scale Mutagenesis Data
Mutations can have profound effects on protein function. For example, mutations can increase or decrease enzymatic activity, influence aggregation propensity, or lead to novel protein functions. Mastery of the rules governing ... -
Learning from the past: Searching for novel TRIM, CypA, and TRIMCyp antiviral factors in primates
(2013-07-23)The evolutionary history and genetic composition of mammals has been strongly influenced by viruses. This is reflected by evolved mechanisms of host defense mediated by restriction factors that are in an arms race to win ... -
Leveraging natural isolates and experimental evolution to characterize biofilm-related phenotypes in Saccharomyces cerevisiae
Biofilm formation is a protective community building behavior in which microbes participate to respond to external stress or colonize new ecological niches. It is a primary mechanism used by pathogenic yeast to persist on ... -
Mapping and Dynamics of Regulatory DNA and Transcription Factor Networks in A. thaliana
Our understanding of gene regulation in plants is constrained by our limited knowledge of plant cis-regulatory DNA and its dynamics. One way in which cis-regulatory elements can be delineated is by their characteristic ...