Engineered organisms need to be functional in fluid dynamic environments. However there is a severe lack of mathematical modeling to effectively determine the feasibility of treatment and deployment of these engineered organisms. Part of my research focuses on creating mathematical models to appropriately simulate and monitor how problematic bacterial communities interact in the presence of bacteriophage, while also observing how fluid dynamic environments affect the transport and infection of bacteriophage. One such fluid-dynamic environment is in pipes, where tough, antibiotic resistant biofilms can form; bacteriophage can be used as a delivery vector of an enzyme that can degrade the extracellular matrix of these biofilms and lead to a novel solution and removal technique. Additionally, Harmful Algal Blooms (HABs) can form in freshwater environments and compromise human health and the ecosystem they form in. Thus, lytically engineered cyanobacteriophage offers a promising approach at remediating HABs in their inherently fluid-dynamic environments.
Student Major(s): Applied Mathematics, Engineering Physics & Applied Design
Advisor: Dr. Margaret Saha
This project explored the biomimetic nature of HASEL actuators as artificial muscles. HASEL stands for hydraulically amplified self-healing electrostatic. These components consisted of plastic pouches made of ziplock bags containing mineral oil which functioned as a liquid dielectric. When a high voltage was applied to either side of the pouches an attractive force compressed one segment of the bag forcing the fluid into another section and creating movement. These components showed potential of being applied in many different robotic ways such as a gripper or robotic legs. HASEL actuators and artificial muscles in general fall under the class of soft robotics which comprises all controllable technology that is deformable and as the name suggests, soft.
Student Major(s): Physics (EPAD) and Computer Science
Advisor: Dr. Jonathan Frey
While you might be familiar with membrane-bound cell organelles such as the mitochondria or endoplasmic reticulum, membraneless organelles are a similar category of organelles that lack a distinct separation from the cytoplasm, or gel that fills the inside of the cell. Membraneless organelles can form spontaneously from the cytoplasm through a process called liquid-liquid phase separation (LLPS) by utilizing the existing nucleic acids, ions, and other salts that are suspended in the cytoplasm. Once formation has occurred, it is assumed that there must be some kind of exchange between the inside of the membraneless organelle and the cytoplasm outside, as well as reactions taking place within the inside of the membraneless organelle, and the fact that there isn't a clear, physical membrane separating the two sides makes the problem all the more interesting to understand. In order to better understand the mechanisms behind membraneless organelles, we applied mathematical equations such as the Cahn-Hilliard equation for phase separation (or how two different phases form) and the Flory-Huggins solution theory to calculate the energies of mixing between different states and the most likely resulting phase separation. Membraneless organelles are relevant to almost any field relating to cellular biology, gene regulation, or even in diseases and aging, and a better understanding of its dynamics and formation is important to further research in these areas.
Student Major(s)/Minor: Computational Applied Math & Statistics - Biology Major, Mathematics Minor
Advisor: Dr. Greg Conradi Smith
This project explores how active aerodynamics can improve the performance of high-speed boats by adjusting aerodynamic components in real time to reduce drag and enhance stability. Active aerodynamic systems use movable surfaces, similar to those found in high-performance cars or aircraft, that automatically adapt to changing conditions during operation. While most vessels rely on hydrodynamics alone, adding this type of real-time aerodynamic control could lead to faster, more efficient, and more stable designs. This research investigates a novel approach with potential applications in racing boats, autonomous vessels, and other high-performance watercraft.
Student Major(s): Physics (EPAD)
Advisor: Dr. Jonathan Frey
Alyssa is a newly discovered satellite phage (phagelet) that triggers the excision of the WMHerbert prophage from the bacterium, Mycolicibacterium aichiense. Because Alyssa is one of the first satellite phages discovered in mycobacteria, little is known about its mechanisms of action. This project aims to bioengineer Alyssa and elucidate its mechanisms of action. Thus far, this project has shown that Alyssa is inconsistent in infecting M. aichiense and Gibson assembly is unsuccessful in assembling Alyssa’s genome. To determine what factors affect Alyssa’s ability to infect M. aichiense, this project employs techniques such as RNAseq, DNA extraction, bacterial genomic sequencing. To assemble Alyssa’s genome in the future, this project will employ techniques such as Goldengate and a TXTL system. This project will contribute to the ultimate goal of gaining a thorough understanding of satellite phages to use them in therapeutic, environmental, and industrial applications.
Student Major(s):Biology and CAMS
Advisor: Dr. Margaret Saha
In every scientific endeavor, a review of current applications and previously completed work is a first step; however, when looking for valuable and essential data, it is difficult and tasking due to the sparsity and inconsistencies from access sites to formatting. One solution would be having a central location with relevant information—such as a database. This project aims to build just that through the extraction, processing, and assembling of relevant aquatic metagenomic samples to create a searchable database that researchers can review and even extract data from, acting as a starting point and supplemental tool. Python was utilized to make web scraping scripts and to merge the final database. Data was extracted from multiple sources, filtered for relevancy, cleaned, and then assembled to provide a useful and easy-to-use database. After filtering, the final database hosts over two thousand relevant samples (with the potential to expand) for researchers to access and utilize.
Student Major(s): Computer Science
Advisor: Dr. Margaret Saha
The cyanobacterium Microcystis aeruginosa is a leading contributor to harmful algal blooms (HABs), which drive significant biodiversity loss in freshwater ecosystems and result in toxin release that is harmful to humans. Scientists have proposed the use of cyanophage (viruses that infect cyanobacteria) as a potential HAB treatment strategy. However, few cyanophages infecting M. aeruginosa have been isolated and sequenced. This project seeks to isolate and engineer novel Microcystis cyanophages from environmental samples in order to improve the feasibility of cyanophage-based HAB treatments. Over 200 liquid phage assays and over 65 agar-based phage plating assays were screened for evidence of bacterial cell death indicative of phage infection. Putative cyanophage plaque formation was observed on two agar plates. Further research will seek to isolate and characterize any phage that may be present and will explore the use of the algicidal bacterium Acinetobacter baylyi as an alternative HAB treatment option.
Student Major(s): Biology, CAMS
Advisor: Dr. Margaret Saha
Bacteriophages, or phages, are viruses specialized in infecting bacterial cells. These small particles will inject DNA into bacteria to hijack cellular machinery, allowing the phage to replicate, killing the bacteria in the process. Their bacterial-killing properties have profound use in modern medicine, where researchers can use specific phages to target specific harmful bacteria in humans. The more we know about bacteriophages, the more useful they become in medicine and beyond.
This project investigates the K3 bacteriophage Neighly using various bioinformatic tools and websites such as DNA Master, NCBI Blast, and the Phages Database. This research answers the questions: “What proteins does Neighly's viral DNA code for?” and “How is Neighly related to other, previously discovered phages?” This valuable information could potentially contribute to the existing international database of phage knowledge.
Student Major(s)/Minor: Undeclared
Advisor: Dr. Margaret Saha
Spider silk is an extraordinarily strong biomaterial built from tightly bundled protein-based fibrils. At the microscopic level, silk is composed of repeating protein based secondary structures that blend flexible alpha-helices with crystalline beta-sheets. This provides the material with both high tensile strength and extensibility, outperforming materials such as Kevlar and high-grade steel. We demonstrate methods to exfoliate delicate nanofibers into solution without compromising structure. Silk fibers from Latrodectus Hesperus were degummed and placed under sonication for a total of 2 hours, with samples taken every 30 minutes. Separately, a 24-hour soak in a 1:1 NaOH/Urea solution caused the silk to release nanofibrils and swell. Scanning electron and atomic force microscopy showed partial exfoliation with both treatments. In the future, we will test other mild chemical treatments and refine our process. These findings will help develop a scalable process for nanofibril production, applicable in lightweight composites and biocompatible scaffolds.
Student Major(s)/Minor: Finn: Chemistry Major, Applied Science: Materials Minor; Zoe: Human Health and Physiology
Advisor: Dr. Hannes Schniepp
This project examines how upregulation and knockout of the Notch Signaling Pathway in transplanted embryonic tissue affects the subsequent fate of the graft and neighboring cells. Notch signaling is a key regulatory mechanism in embryonic development, playing a role in cell fate and differentiation. Previous studies in the Saha Lab have examined the ability of embryos of Xenopus laevis to recover following mRNA construct-mediated perturbations of this pathway. Researchers found embryos can respond and correct these perturbations to an extent in early stages. Other work done in the Saha Lab has demonstrated how embryos can aptly respond to physical perturbations up to the mid-gastrula stage. This study aims to understand the mechanisms that regulate how the Notch Signaling Pathway controls cell fate, using transplantation of the neural tube as a means to better elucidate the underpinnings of embryonic trauma recovery and subsequent fate correction.
Student Major(s): Neuroscience
Advisor: Dr. Margaret Saha
Lysogenic bacteriophage viruses inject and incorporate their genomes into bacterial hosts, where the genome resides largely dormant and replicates with the cell until triggered. This process can potentially be repurposed for gene delivery in medical and environmental settings, so it is essential to understand phage-host interaction control mechanisms. Antirepressors are a type of protein that impact the excision (exit) of the viral genome by binding to repressors, but they are not well understood. Present in many phages and satellite phages, they are a control mechanism utilized by both the bacterium and phage. This project employs features in AlphaFold, an AI protein modeling software, to determine the 3D structure of antirepressors in various sequenced phages and satellite phages (phagelets). Binding analysis will show if and how the antirepressors bind with coordinating repressors and any common structure. This will help improve understanding of phage-host interactions in research using phages for gene delivery.
Student Major(s):Computer Science, CAMS
Advisor: Dr. Margaret Saha
Microbes are abundant in all natural environments and play key roles in ecological processes as well as in bioengineering and synthetic biology applications. However, microbes behave drastically differently in labaratory environments compared to dynamic, flowing environments where physical forces are acting upon them. This project investigates the transcriptional basis of these differences by compiling and analyzing existing transcriptomic datasets spanning diverse bacterial taxa and environmental conditions. The datasets include conditions where bacteria are exposed to physical forces such as shear stress, enabling identification of gene expression patterns linked to mechanical stressors. Comparative analyses across genera and species are used to determine conserved and divergent responses to physical stress. By uncovering shared transcriptional strategies, this research aims to advance understanding of microbial adaptation to flowing environments and inform the design of microbial systems for engineered applications in flowing environments.
Student Major(s): CAMS Math Bio, Biology
Advisor: Dr. Margaret Saha
Bacteriphages, or viruses that infect bacteria, must decide whether to replicate immediately or remain dormant within the host genome. If choosing to remain dormant in the host bacteria, also known as the lysogenic cycle, phages must highly regulate their stable state in the genome. The antirepressor protein plays an important role in regulating this phase of viral replication, yet the diversity and function of these proteins are not well understood across many different phages. In this project, I examined the antirepressor protein in the mycobacteriophage DocMcStuffins and its role in the infection of Mycobacterium smegmatis. Using wet-lab experimentation, I investigated how the antirepressor gene could potentially control the switch between the lysogenic and lytic cycles of phages. The findings of this study contribute to the overall understanding of phage life cycle regulation and phage-host interactions, providing key insights into future work with phage therapy.
Student Major(s)/Minor: Biology Major, Chemistry Minor
Advisor: Dr. Margaret Saha