The goal of this project was to design and create a genetic construct that would allow for <br/>tumor growth to be induced in the center of the wing imaginal disc of Drosophila larvae, the <br/>R85E08 domain, using a heat shock. The resulting transgene would be combined with other <br/>transgenes in a single fly that would allow for simultaneous expression of the oncogene and, in <br/>the surrounding cells, other genes of interest. This system would help establish Drosophila as a <br/>more versatile and reliable model organism for cancer research. Furthermore, pilot studies were <br/>performed, using elements of the final proposed system, to determine if tumor growth is possible <br/>in the center of the disc, which oncogene produces the best results, and if oncogene expression <br/>induced later in development causes tumor growth. Three different candidate genes were <br/>investigated: RasV12, PvrACT, and Avli.

The purpose of the project is to create a survey that will be sent out to thousands of members of the Global Alliance for Genomics and Health (GA4GH) to update GA4GH's Catalogue of Genomic Data Initiatives online. GA4GH's Catalogue of Genomic Data Initiatives has not been updated in several years, leading to outdated and incorrect information. The survey will be used to gather information from genetic groups worldwide to update and increase the amount of data in the Catalogue on the GA4GH website. The questions were created in collaboration with GA4GH and the Human Pangenome Reference Consortium (HPRC). The actual survey was designed on Qualtrics.

This project is an investigation of the gene by environment (GxE) interactions’ effect on substance use outcomes among refugee communities. Substance use disorders (SUDs) are a major public health concern, affecting individuals and communities worldwide. The etiology of SUDs is complex, involving a combination of genetic, environmental, and social factors. In recent years, there has been growing interest in the role of gene by environment interactions in the development of SUDs, particularly in vulnerable populations such as refugees. Refugee populations are exposed to a range of environmental stressors that may interact with genetic factors to increase their risk of SUDs. However, a number of studies describe a “refugee paradox,” where despite having been exposed to risk factors that can lead to SUDs, they are less likely to develop SUDs. Understanding these gene by environment interactions in refugee communities is crucial for not only understanding this phenomenon, but developing effective prevention and treatment strategies for this population. This thesis aims to investigate the gene by environment interactions underlying substance use in refugee communities and to analyze different methods for gene by environment analyses, ultimately determining which method is best suited for this population.

Most protein-coding mRNAs in eukaryotes must undergo a series of processing steps so they can be exported from the nucleus and translated into protein. Cleavage and polyadenylation are vital steps in this maturation process. Improper cleavage and polyadenylation results in variation in the 3′ UTR length of genes, which is a hallmark of various human diseases. Previous data have shown that the majority of 3’UTRs of mRNAs from the nematode Caenorhabditis elegans terminate at an adenosine nucleotide, and that mutating this adenosine disrupts the cleavage reaction. It is unclear if the adenosine is included in the mature mRNA transcript or if it is cleaved off. To address this question, we are developing a novel method called the Terminal Adenosine Methylation (TAM) assay which will allow us to precisely define whether the cleavage reaction takes place upstream or downstream of this terminal adenosine. The TAM Assay utilizes the ability of the methyltransferase domain (MTD) of the human methyltransferase METTL16 to methylate the terminal adenosine of a test mRNA transcript prior to the cleavage reaction in vivo. The presence or absence of methylation at the terminal adenosine will then be identified using direct RNA sequencing. This project focuses on 1) preparing the chimeric construct that positions the MTD on the mRNA cleavage site of a test mRNA transcript, and 2) testing the functionality of this construct in vitro and developing a transgenic C. elegans strain expressing it. The TAM assay has the potential to be a valuable tool for elucidating the role of the terminal adenosine in cleavage and polyadenylation.