Interdisciplinary – Page 18 – UROP Spring Symposium 2021

Interdisciplinary

Multimodal Retinal Imaging of Usher Syndrome Animal Model of Photoreceptor Degeneration

Emilie Gilligan Pronouns: she/her Research Mentor(s): Yannis Paulus, Assistant Professor, Tenure Track Research Mentor School/College/Department: Ophthalmology and Visual Sciences, Michigan Medicine Presentation Date: Thursday, April 22, 2021 Session: Session 5 (3pm-3:50pm) Breakout Room: Room 12 Presenter: 5 Event Link Abstract For privacy concerns this abstract cannot be published at this time. Authors: Emilie Gilligan, Ashley […]

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Black Families After Civil War – Creating Network of Care

How did African American families survive and care for themselves during the transition for slavery to freedom? Our research investigates this question by following the lives of widows after the Civil War. After the war, the wives of Black soldiers who died filed for pensions from the federal government. These files include biographical information of the families and testimonies from those that could attest to the fact that the woman filing for a pension was married and had found support or taken up with a new husband. The goal of this research is to understand how Black women formed networks of care and how Black families and friends maintained ties from slavery, to freedom–through the Reconstruction period and into Jim Crow period. This research compiles genealogical data from the census, analyzes secondary literature, and examines pension files. We find that Black women held closely to their immediate familial relationships and their friends through common experiences and interactions. However, separation of Black families and friends due to geographical movement caused a strain on relationships. We hope to uncover more intimate information regarding the families being researched. The networks created among Black people represent the past and contemporary need for a sense of community among African Americans.

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Bioinformatics study on genetic diseases

Proteins are responsible for much of the functions and regulation of living organisms and their body systems. Understanding protein function has much to do with protein structure, thus, knowing what form proteins take is very useful. There are millions of different types of proteins, many of which are essential for human survival. Current ways to determine protein structure require knowledge of the genetic DNA sequence, which can later be translated into an amino acid sequence, thus revealing the shape through chemical properties. However, this study aims to create a program that can accurately predict protein structure without knowledge of the amino acid sequence. Instead, cryo-EM density maps are utilized to map the protein structure. The density maps are created utilizing convolutional neural networks (CNN), which are used to predict key atoms. These deep learning techniques are applied to create the program that can accurately predict a protein structure. This research is valuable because other scientists who require knowledge of protein structure could use it, especially if they do not have access to a specific genetic sequence they need. Next steps include perfecting the program such that the predictions reach the threshold for accuracy.

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Golgi biogenesis, function, and deffects in diseases

It has been observed that the Golgi apparatus is involved in signaling and in cell adhesion and migration. Additionally, the unique Golgi stacking structure is an essential aspect of Golgi function. Our lab has demonstrated that GRASP55 and GRASP65 are required proteins for Golgi stacking. It has also been shown that integrin a5ß1 is downregulated in GRASP KO cells and that integrin a5ß1 is involved in Epithelial-to-mesenchymal transition (EMT). Using this information, our lab is working to find a possible mechanism that shows that Golgi stacking formation is required in EMT.

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Modeling Molecular Pathogenesis of Idiopathic Pulmonary Fibrosis associated Lung Cancer (IPF-LC) in mice

Lung diseases are prolific killers in the United States each year. Of the major respiratory illnesses and cancers, lung cancer (LC) and idiopathic pulmonary fibrosis (IPF) are especially notable. In the US alone, there is estimated to be 250,000 new cases of lung cancer diagnosed annually, and around 130,000 patients die from the disease as well (Cancer.org). Meanwhile, IPF affects close to 200,000 people in the United States with a 3-5 year survival rate of 50% (National Heart, Lung, and Blood Institute). For each of the two diseases, treatment options are very different, making it especially difficult to provide sufficient care. In addition, around 22% of IPF patients will go on further to develop non-small cell lung carcinoma (NSCLC), or lung cancer (The Lancet). While it is not completely clear as to why this happens, it is likely due to increased inflammation in the lungs, providing an optimal ground for tumor growth.

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Skilled Reaching Performance in a Model of DYT1 Dystonia

DYT1 Dystonia is a neurological condition that causes abnormal, sustained twisting postures, resulting from a Delta-E mutation in the torsinA gene. Mice with this genotype have few motor abnormalities, making it difficult to test treatments in this model. However, previous attempts to phenotype these mice used simple motor assays. The project in which I am assisting is the first project aiming to find the relationship between mice with a DYT1 Dystonia mutation and their ability to perform skilled reaching, a demanding task that requires fine motor coordination. To gather results, I am scoring hundreds of videos of mice reaching for pellets on a pedestal to see how the DYT1 genotype impacts a mouse’s ability to reach. In scoring videos, I watch each video numerous times and give it a score 1-10 based on how/if the mouse reaches for and grasps the sugar pellet. I put these results in a spreadsheet, and will analyze them to determine if DYT1 mice are significantly impaired compared to wildtype mice. Because this is a brand new project, there have been no results. I just started scoring videos this week, however, the lab suspects that these will have issues obtaining the pellet This would suggest that they have subtle motor abnormalities that could be used to test therapies. The results of this experiment are important because they can be the first steps in finding treatment for humans with DYT1 Dystonia.

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Protein Structure Prediction Using CryoEM Density Maps

The goal of my research was to prepare my own dataset, which includes a training set and a test set, and build my own neural network in order to predict protein backbone with cryo-EM density map as my input. In order to get to know more about deep learning and neural networks, I completed 2 coursera courses recommended by my mentor to gain the skills needed to start building my own neural network by using python software. I also read one major literature that focused on cryo-EM technologies to further learn about how incorporating density maps of proteins can provide us with important structural information of proteins. A density map can be obtained using cryo-electron microscopy in order to obtain atomic-resolution models of the protein, including the coordinates of the backbone protein atoms. However, the index/connection of these atoms are lost during the process of obtaining the density map. Predicting the protein backbone will allow us to restore the connectivity of the backbone atoms in the protein and improve the CR-I-TASSER, which incorporates both deep learning and I-TASSER force fields in order to provide accurate structures of the protein backbone.

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De novo design of PD-L1 protein-based inhibitor

Certain types of proteins, such as PD-L1, enable a cancer cell to bypass T-cell immune checkpoints. This results in cancer cells being undetected in the body and time for cancer cells to grow and multiply. This investigation attempts to create a favorable PD-L1 protein inhibitor so that the cancer cells that it resides on will be detected by the body’s immune response. Through the usage of PERL programming, EvoDesign, and FoldDesign, the best protein inhibitor will be determined by its binding affinity to the protein and its stability and will be tested in a wet lab in the future. The results of this study will eventually be used and tested to see whether the designed inhibitor is suitable for usage.

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Altered Kynurenine Pathway in Aortic Patients is Linked to CKD Atherosclerosis

Skyelar Herriman Pronouns: she/her/hers Research Mentor(s): Anna Mathew, Assistant Professor Research Mentor School/College/Department: Internal Medicine/ Nephrology, Michigan Medicine Presentation Date: Thursday, April 22, 2021 Session: Session 5 (3pm-3:50pm) Breakout Room: Room 11 Presenter: 5 Event Link Abstract For privacy concerns this abstract cannot be published at this time. Authors: Skyelar Herriman, Julian Meza, Biaoxin Chai,

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Scoping review on the impact of type 2 diabetes self management programs in Asian-Americans

Type 2 diabetes (T2D) is among the top reasons for deaths in Asian-Americans (AA). While this group consists of people from over 20 different countries, existing research often does not reflect the diversity and differences among AA, including many existing diabetes self-management programs (DSMP). No previous studies have compared existing DSMPs targeting AA. This scoping review includes adult AA participants and T2 DSMPs. DSMPs were defined as managing an individual’s condition, including self-care, symptom management, family management, medical-management, emotional management, or resource utilization. Keywords used to search for relevant articles included type 2 diabetes, Asian Americans (and its different subpopulations), and self-management. We searched for relevant articles with no data range in six databases, yielding 2581 results. DistillerSR was used to screen and extract data. After screening for titles and abstracts, 311 articles were included in the full-text screening. After screening the full-text articles, 31 articles were included in the final analysis. Articles were excluded if they were non-primary research studies, did not focus on T2D or AA adults, and did not include DSMPs. Data on different interventions and outcomes were extracted and analyzed using a charting form. We hypothesized that there is a need for more research focusing on minority subgroups. We also hypothesized that there is a need for more specialization of DSMPs to overcome many barriers AA face in healthcare, so that specific cultural and ethnic needs are addressed. Improved understanding of existing research may improve and guide future research in developing T2D self-management interventions for AA.

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