Author: orandall

Many animals rely on microbial symbionts to help them gain sufficient nutrients, provide protection from predators and pathogens, or allow them to live in otherwise inhospitable environments. Studying these relationships can be difficult as it is often impossible to separate the microbes from their host. As a result, understanding of the mechanisms that underly these relationships has been limited by the inability to manipulate both host and symbiont independently. Kissing bugs are insects that feed exclusively on vertebrate blood and serve as host to symbiotic bacteria, that help them successfully develop and reproduce. These bacteria also can be cleared from the kissing bugs and infected with new bacteria. The symbiont bacteria can also be grown outside of the insect and can be genetically altered. This system, thus, provides a unique opportunity to experimentally manipulate the host and symbiont, to identify and characterize factors that support the symbiosis. The research will focus on genes involved in symbiont colonization of the host, host and symbiont genes involved in the exchange of nutrients, and interactions of the host immune system and the symbiont. Given the ubiquity of animal-microbe symbioses, this research will illuminate mechanisms that may govern host-microbe interactions in other less-tractable systems. Along with the proposed research, this project will also provide research experience and training to high school teachers. This experience will be paired with curriculum development to incorporate host-microbe interactions into the teachers’ classrooms.

Experimental manipulation of host-microbe systems has been limited by inability to separate highly integrated partners or difficulties disentangling the effects of individual members in highly complex communities. Triatomine kissing bugs harbor essential symbionts in their gut which are environmentally acquired each generation, allowing for generation of bacteria-free, axenic insects, which can then be experimentally inoculated with bacteria. This work leverages the unique features of this system – ability to generate axenic and gnotobiotic insects, low-complexity microbiomes, and molecular tools – to delineate the mechanistic basis of symbiosis. Transposon mutagenesis will be used to identify genes in the symbiont Rhodococcus rhodnii that are essential for symbiosis followed by generation of knockout strains of R. rhodnii lacking symbiosis-promoting genes. Knockout strains will be used for bioassays to characterize the role of the gene-of-interest in the relationship. The role of the host immune system in regulating bacterial abundance will be assessed, examining both humoral and cellular immune responses to symbionts. Lipid metabolism genes including fatty acid synthases and fatty acid CoA reductases have been identified as differentially expressed in axenic and gnotobiotic insects. Liquid chromatography and mass spectroscopy will be applied to understand how symbiotic bacteria shape the lipidome of kissing bugs while silencing of specific lipid genes will reveal the role of these genes in lipid metabolism and host fitness. The proposed work will shed new light on the evolution of host-symbiont interactions and serve as a framework for exploring systems which are less amenable to experimental manipulation.

• Funder: NSF
• Amount: $1,067,638
• PI: Kevin Vogel

PROJECT SUMMARY/ABSTRACT Ca2+ ions impact almost every aspect of cellular life. Ca2+ signaling begins with the opening of Ca2+ channels in either the plasma membrane (PM) or the endoplasmic reticulum (ER) and results in a dramatic increase in the physiologically low (<100 nM) cytosolic Ca2+ levels. The temporal and spatial Ca2+ levels are exquisitely regulated and enable the precise and specific activation of critical biological processes like changes in gene expression, cell differentiation, muscle contraction, fertilization, or secretion of neurotransmitters to name a few. Ca2+ signaling regulates pathogenic pathways of apicomplexan parasites like Toxoplasma gondii which infects approximately one third of the world’s population. T. gondii is an opportunistic pathogen of immunocompromised patients like HIV-infected individuals, fetuses, and organ transplant recipients. As an obligate intracellular pathogen, T. gondii replicates inside cells and the clinical manifestations of toxoplasmosis are a direct result of its growth within cells and its dissemination. T. gondii relies on Ca2+ signals for the stimulation of specific features of its infection cycle and several Ca2+ signaling elements play essential roles in its parasitic cycle. However, the fundamental elements that initiate Ca2+ signals in T. gondii are largely unknown yet are likely essential for its viability and virulence. Discovery and characterization of the molecules that initiate Ca2+ signaling in T. gondii are hence central for the understanding of its pathogenesis. Active egress of T. gondii from host cells is critical for dissemination of the infection and our prior work has provided conclusive evidence that there is a cytosolic Ca2+ peak preceding egress. This parasitic cytosolic increase arises from release from intracellular stores, likely the endoplasmic reticulum. It is puzzling, however, that intracellular parasites replicate surrounded by the low host cytosolic Ca2+ but still store sufficient Ca2+ in their ER to trigger egress. Upon host cell rupture, extracellular Ca2+ influx across the PM contributes to a second Ca2+ peak enhancing motility of parasites, which then exit and seek another host cell to invade. Our hypothesis is that PM Ca2+ entry is essential for refilling of intracellular Ca2+ stores, and both intra and extracellular sources are necessary for triggering the cascade of molecular events that lead to the stimulation of parasitic functions like motility, secretion of adhesins, invasion of host cells, egress and dissemination. In this proposal we aim to characterize the proteins that enable PM Ca2+ influx. There is almost no information about the functional characteristics and roles of Ca2+ channels in T. gondii. This lack of knowledge could be due to lack of appropriate tools, techniques, and training in electrophysiology within the molecular parasitology field. We address this void with a collaboration with a mammalian electrophysiologist and a modeler. Channels are critical for the successful unicellular life of parasites, and they could be targeted by many therapeutically useful agents. Ion channels remain significantly under-exploited as therapeutic targets, even more so as antiparasitic agents.

• Funder: NIH
• Amount: $3,024,775
• PI: Silvia Moreno

Driven by the demand in artificial intelligence (AI) in manufacturing, in partnership with the Russell Innovation Center for Entrepreneurs (RICE), we propose the creation of an advanced mobile manufacturing outreach laboratory that serves as a physical and digital gateway for current and future entrepreneurs to gain exposure to state-of-the-art technology, generate value-adding ideas, and receive formal training. The mobile laboratory will provide exemplary training modules and connected equipment where they are needed most, among communities of entrepreneurs that are historically underrepresented in manufacturing and thus have the greatest untapped potential for advancing the industry and at the same time promoting job growth through small business opportunities. The mobile laboratory will provide participants with three types of educational delivery mechanisms: (1) state of the art technology vignettes, (2) modules for participants to complete on-site, and (3) an off-site module participants can use for virtual reality (VR) based training that includes an entrepreneurial component.  The Vignettes will be developed by RICE while the on-site and off-site modules will be built, developed, and maintained by UGA.  The three mechanisms are meant to offer participants an opportunity to understand, apply, and create manufacturing AI projects.  Further, the offerings provide participants with a varying level of engagement with the mobile laboratory depending on their implementation readiness.  The goal is to cater to a wide range of participants while providing multiple modes of experiences, spanning multiple educational goals.

• Funder: US Department of Commerce via the Russell Innovation Center for Entrepreneurs
• Amount: $3,600,000
• PI: Jaime Camelio

Parents are typically viewed as an essential part of the school and community; however, Black mothers are seldom positioned this way. As such, this study expands on a year-long research study that centered the onto-epistemologies of Black mothers as they envisioned an education for their children that moves beyond simply passing. While the initial study focused on Black mothers in the Southeastern region of the United States, this study focuses on Black mothers in the Greater Toronto Area (GTA) as they negotiate and navigate educational policies that aim to address anti-blackness in schools. This study recognizes the geopolitical differences that shape educational policy and lived experiences while also building on Black Diasporic work. Resultantly, the proposed study seeks to explore the extent to which Black mothers have been included and involved in the development of education policies related to antiblackness. From January 2023 to December 2024, this Spencer Grant would support research working with Black mothers in GTA as they navigate and negotiate educational policies that aim to address antiblackness in their children’s schools. The analytical arguments derived from the experiences of these mothers may offer insight into educational policy around anti-blackness, which could serve to inform various educational stakeholders.

• Funder: Spencer Foundation
• Amount: $71,588
• PI: Tianna Dowie Chin

Mixotrophs are essential components of the Antarctic planktonic community able to photosynthesize and also ingest small particles like bacteria to meet their nutritional needs. This project aims to understand the physiological response of mixotrophs exposed to micronutrient limitation in the Southern Ocean, specifically iron, manganese and simultaneous limitation of more than one trace metal, or colimitation. Such environmental conditions are characteristic of the Southern Ocean and can only be tested with local algae. The Principal Investigators hypothesize that under trace metal colimitation, some mixotrophs will have a competitive advantage by increasing their ability to consume particles to obtain energy and trace metals from their prey. Given the lack of understanding of how mixotrophs have adapted to the micronutrient limitation, the researchers propose studies with microalgal cultures isolated from the Southern Ocean; they will measure growth responses, consumption behavior, changes in cellular chemistry and transcription of genetic material in response to iron and manganese limitation. This project benefits the National Science Foundation goals of understanding Life in Antarctica and adaptation of organisms to this extreme environment. Society will benefit from the training proposed, whereby students from rural colleges will be instructed in computer coding and scientific data analyses. Furthermore, this work will support one graduate student, two undergraduate summer interns, and two early career scientists.

The Principal Investigators hypothesize that under Fe-Mn colimitation, some mixotrophs will have a competitive advantage by increasing their grazing rates to obtain energy, Fe, and Mn from their prey. Given the lack of understanding of how mixotrophs have adapted to seasonal changes in the availability of these micronutrients and how they influence mixotrophic growth dynamics, the PIs propose culture studies to measure growth responses, grazing behavior, and changes in elemental stoichiometry in response to Fe and Mn limitation. Transcriptomic analyses will reveal the metabolic underpinnings of trophic behavior and micronutrient stress responses, with implications for key biogeochemical processes such as carbon fixation, remineralization, and nutrient cycling. Results are expected to clarify the ecological roles of Antarctic mixotrophs and elucidate the adaptations of Southern Ocean organisms to their unique polar ecosystem following the 2015 Strategic Vision for Polar Programs. This work will support one graduate student, two undergraduate summer interns, and two early career scientists. A series of virtual coding and bioinformatic workshops will be organized, in which basic principles of coding, and data processing used in the proposed analysis will be taught to undergraduate students. Small colleges in rural areas will be targeted for 8 modules on bioinformatics training.

• Funder: NSF
• Amount: $379,674
• PI: Natalie Cohen

GlyGen is a maturing (five years old) knowledgebase that accumulates data in the glycobiology domain and connects it with other data types. GlyGen is unique; no other present or prior informatic resource has undertaken such an integrative mission. In part, the lagging growth of accessible knowledge in the glycobiology domain, compared to other -omics or biomedical research fields, reflects the inherent complexity of glycan structures, which, unlike genes and proteins, exist in branched and isomeric forms whose biosynthesis is not attributable to well-characterized, template-driven processes such as transcription or translation. Rather, glycan biosynthesis is mediated by the regulated expression of ensembles of glycosyltransferases, substrate transporters, and secretory pathway regulatory mechanisms that together generate dynamic cell- and tissue-specific patterns of protein and lipid glycosylation. In addition, each glycosylation site on a glycoprotein may routinely be modified by one of an ensemble of glycan structures, a glycoprotein feature called microheterogeneity. Importantly, microheterogeneity is not random, but reflects the intrinsic biosynthetic capacity of specific cells and tissues and may be modified by disease. These structural and biosynthetic complexities are essential contributors to the tissue- and disease-specific functions of glycans and glycosylation, and, therefore, need to be captured and represented in knowledgebases in a way that they can be queried and linked to other types of data. GlyGen aims to expand its underlying data model to accommodate new and more complex datatypes, augmenting and integrating new data types, and implementing robust modeling, unified procedures, and tools to improve discovery and exploration of glycan and glycoconjugate data. Enhancement of the overall resource 

functionality will be achieved through front-end improvements to accommodate user preferences and ensure exceptional data communication and visualization. Improving the interconnectivity of GlyGen and its partner databases as well as enhancing data-sharing across resources will continue to be core principles of the GlyGen project. All resulting harmonized data will be available through highly permissive licenses for easy integration into other resources, such as NCBI, EBI, SIB and other international efforts, as well as for easy repurposing by independent researchers, educators, bioinformaticians, and commercial entities. By the end of the next project period GlyGen expects to become the go-to, well-integrated 

resource for glycoscience data, similar to existing protein and genomic resources and serving the same broad community of biomedical researchers.

• Funder: NIH
• Amount: $5,397,508
• PI: Michael Tiemeyer

The focus of this project is investigating a variety of questions in low dimensional topology, which is the study of shapes of spaces with dimension at most four. Central in this subject is the study of knotting and linking of circles in three-dimensional spaces, called knot theory. For instance, knots and links can be used to construct three- and four-dimensional spaces. Low dimensional topology and knot theory have various connections to cosmology and physics (the shape of the universe and string theory), and biochemistry (the knotting behavior of DNA molecules). Unintuitively, many classification questions in topology are harder in dimensions three and four, and over the past three decades, topologists have developed modern tools (with roots in physics) for studying these questions. Two examples of such tools are Heegaard Floer invariants, which grew out of gauge theory, and Khovanov homology, which has roots in representation theory. This project will further develop these invariants and investigate their similarities and relations. Moreover, it will harness their power to study symmetries of surfaces (two-dimensional spaces), in connection with hyperbolic geometry and dynamics, and will investigate several fundamental questions in low-dimensional topology such as finding the minimum number of times a knot must cross itself to become unknotted.

In parallel, this project aims to make mathematics and in particular topology accessible to a broad audience, through educational activities at all levels with an emphasis on diversity and inclusion. These activities include, establishing a Math Circle program in the Athens-Clarke County public library and organizing summer Math Camps for high school and middle school students, running a summer research experience project for undergraduate students and a topology summer school for graduate students and postdocs. The major goals of this research program are organized around four areas. First, developing new invariants for studying spatial graphs and graph concordance. The main tool will be a generalization of (minus) Heegaard Floer homology called, tangle Floer homology. Studying spatial graphs up to concordance has applications in studying equivariant concordance between knots, and strong concordance between links. Second, studying mapping class group and extensions of surface diffeomorphisms over handlebodies using another generalization of Heegaard Floer homology, called bordered Heegaard Floer homology. Third, further developing the bordered Heegaard Floer homology tools by generalizing and refining the contact invariant defined by the PI and her co-authors and use it to address open questions in contact topology. Lastly, the PI focuses on connections and similarities between Khovanov homology and Heegaard Floer invariants, with the three major goals of defining new concordance invariants to study smooth 4D Poincare conjecture, finding new lower bounds for the unknotting number and developing new invariants for transverse knots.

• Funder: NSF
• Amount: $549,999
• PI: Akram Alishahi

This CAREER project focuses on the study of surfactant compounds in atmospheric aerosol and their effects on particle hygroscopic growth. Field collections and laboratory experiments using high resolution chemical and physical analyses will be used to assess the influence of surfactant molecular composition and associated properties on the hygroscopic growth of atmospheric particles. Hygroscopic growth can alter particle size and composition, both of which are important determinants in the influence of aerosol particles on visibility and human health.

The effect of surfactants on particle hygroscopic growth is expected to be nonlinear and dependent on the surfactant molecular composition, structure, and critical micelle concentration. The experimental plan will address the following questions: (1) What are the compositions, structures, and interfacial properties of surfactants in atmospheric aerosol particles? How do these surfactant characteristics vary as a function of particle size and air mass source region (e.g., natural, anthropogenic, marine, aged influences)? (2) What effects do surfactant structure, composition, and interfacial properties have on the hygroscopic growth of submicron and supermicron aerosol particles? Chemical and physical measurements of aerosol particles collected as part of two field campaigns at the Skidaway Institute of Oceanography, on the coast of Georgia, will be made during two seasons to capture seasonal variability. Laboratory experiments will also be conducted to measure the hygroscopic growth of model laboratory-generated aerosol particles to determine the influence of the surfactant fraction directly. Multivariate statistics will be used to determine the surfactant properties in different particle types.

The education and outreach plan includes working with high school students to collect local air quality measurements, developing a new laboratory course to explore the principles of analytical chemistry through measurements of aerosol chemistry, and conducting a first-year research seminar course and a summer research experience for undergraduate students.

• Funder: NSF
• Amount: $730,100
• PI: Amanda Frossard