Syracuse University

NSF Awards · FY 2024 · 2024-09

This award will further explore new physics at the LHCb experiment at CERN. The work will continue developing the detector and algorithms that could lead to new discoveries in B physics that could shed light on fundamental questions such as why the universe is dominated by matter rather than antimatter. This work builds on the ongoing work of the Syracuse group on the Upstream Tracker (UT), a key component of the LHCb experiment. This UT plays a crucial role in identifying b quarks in the collisions at LHCb. The group is developing Machine Learning and Artificial Intelligence to further refine the identification process in this b-quark analysis. This award will also provide R&D focused on the electronics that optimize the performance of the new calorimeter considered for the last chapter of LHCb to fully exploit the unique opportunities of the HL-LHC. This instrumentation work supports the technological leadership of the US, which ultimately is also a strong factor in ensuring our National Security. This group will also work on the education of the next generation of STEM professionals, thoroughly aligned with the goals of promoting national health, prosperity, and welfare. The team includes undergraduate, graduate, and post-doctoral research associates. In addition, they will engage high-school students from city schools in summer internships. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2024 · 2024-09

To make quantum computers practically useful, the underlying building blocks, called qubits, must be protected from the environment so that no errors occur during the computations. The current superconducting qubit technology is limited by the time it takes to check and fix these errors. A major roadblock to improving the performance of superconducting quantum processors comes from the inefficiencies in determining the quantum states of individual qubits because of the tendency of the qubits to leave the intended states during the measurement process. This project focuses on understanding the underlying physical mechanisms that govern the qubit transitions during the measurement process and aims to develop and experimentally verify methods for predicting these transitions in the state-of-the-art superconducting qubits to improve the performance of modern quantum processors and to expand the capabilities of superconducting quantum technologies. The societal benefits of the project include advancing the fundamental understanding of measurements in quantum mechanics and fostering novel design paradigms in the development of quantum devices and sensors. Graduate students working on the project will acquire theoretical and experimental skills essential for long-term economic growth driven by advanced technologies. The error rates required for performing practically useful quantum computations must be significantly below the rates achievable with the currently available physical qubits. Quantum error correction offers a way to effectively reduce error rates by encoding logical qubits within an array of physical qubits. The present-day implementations of the error correction codes with superconducting qubits are largely limited by the time that it takes to readout and reset the qubits used to detect the errors in the remaining part of the circuit. Further progress in shortening the readout time and increasing the measurement fidelity of the widely used dispersive qubit measurement scheme is hindered by the measurement-induced qubit transitions into the out-of-computational space. This project aims to provide a universal framework for systematically identifying the measurement-induced transitions and analyzing the limitations imposed on the dispersive readout by these transitions. The theoretical framework for estimating the maximum number of photons will be experimentally verified in model qubit systems such as transmons and fluxonia. Once verified, it will be applied to optimize the dispersive readout of fluxonium qubits. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2024 · 2024-09

This two-year Exploring Theory and Design Principles (ETD) project will engage culturally and linguistically diverse resettled refugee and immigrant middle school students in co-designing culturally relevant and place-based STEM learning experiences through immersive digital storytelling. During the digital storytelling co-design process, participants will expand their STEM disciplinary knowledge and skills in agriculture, environmental science, and entry-level computer coding. The goal of this project is to increase participants’ STEM learning, identity, and self-efficacy and to broaden their interests in STEM career pathways. The project is distinguished by four key features: (1) an interdisciplinary approach in which STEM learning is integrated into an immersive digital storytelling process; (2) a focus on culturally relevant and place-based STEM learning experiences integrating two contexts of participants’ lived experiences: food stories connected to diverse countries of origin and environmental science stories integral to the agricultural community in their new homes, (3) a participatory design whereby participating students co-design digital stories with researchers, graduate mentors, undergraduate near-peer mentors, and community members; and (4) a community partnership where participants’ learning experiences are enhanced through local farm industry mentorship and museum exhibit residency opportunities. Forty resettled refugee and immigrant middle schoolers in Syracuse, New York, will participate in the program in two cohorts, with one cohort for each year of the project period. Within the general lens of the sociocultural framework, this project incorporates asset-based approaches with community-based participatory research to support refugee and immigrant youth’s STEM aspirations. The research team will investigate a set of questions focusing on whether and how the proposed program intervention supports culturally and linguistically diverse resettled refugee and immigrant youth. These questions include: (1) Is the proposed program intervention effective in supporting STEM learning for participating learners? And in what ways? (2) Is the proposed program intervention effective in supporting STEM identity and self-efficacy for participating learners? And in what ways? (3) Is the proposed program intervention effective in supporting STEM career interests for participating learners? And in what ways? (4) Are there challenges that participating youth encounter during the project? If so, what strategies can be used to overcome them for future iteration and scale-up of the program? The project will use a primarily qualitative ethnographic method to explore these research questions, including participatory visual techniques, observations, interviews, video recordings, reflection notes, and project artifacts. In addition, pre- and post-surveys will be conducted to measure participants’ change in STEM self-efficacy and career interests. Deliverables will include (1) participants’ immersive digital stories, which can serve as learning tools in various formal and informal settings; (2) two sets of modules/curriculum, one for facilitators and one for participants, supporting the co-design process, which will be made available to educators through multiple forms of dissemination; and (3) a practical guide for using community-based research to involve refugee and immigrant youth in STEM based on the project findings. Research findings will be disseminated through a project website as well as conference presentations and journal publications. All program materials will be made free and publicly accessible so that other educators, designers, and researchers can replicate or modify to support underrepresented learners in STEM. This project is funded by the Innovative Technology Experiences for Students and Teachers (ITEST) program, which supports projects that build understandings of practices, program elements, contexts and processes contributing to increasing students' knowledge and interest in science, technology, engineering, and mathematics (STEM) and information and communication technology (ICT) careers. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2024 · 2024-09

Many of our society’s most pressing challenges – including food security, sustainability, and supporting aging populations – will require breakthroughs in biotechnology and bio-inspired science. This National Science Foundation Research Traineeship (NRT) award to Syracuse University will train a new generation of scientists and engineers who can evaluate and harness complex systems, such as biological tissues or next-generation materials, to drive intelligent responses such as sensing, actuating, and learning, leading to breakthrough technologies. The project anticipates training 115 PhD students, including 37 funded trainees, from fields that span the life and physical sciences and engineering. The innovative, team-based curriculum and research program will build STEM workforce capacity by training people who thrive on high-performing interdisciplinary teams, where each member of the team contributes unique and deep disciplinary expertise while still communicating their knowledge across a diverse team to drive discoveries not possible within a single discipline. This project will train Ph.D. students to identify and characterize emergent behaviors through several applications that cross-cut biology and materials design. Since biological organisms harness the emergent behavior of components at small scales to generate intelligent structures that perform tasks at large scales, similar principles can be used to design new intelligent materials and devices. The program curriculum supports the interaction between biology and material design fields by first training students in core disciplinary competencies, then providing explicit curricular training in interdisciplinary team building via the evidence-driven “Team-Based Learning” paradigm, and ultimately engaging students on research teams with world-expert faculty from diverse disciplinary backgrounds. These teams will approach difficult problems from new perspectives and transfer useful tools and techniques between the life sciences and materials design. The project also provides longitudinal entrepreneurship training so that students are able to commercialize their discoveries and work in industrial settings. This training will help students bring their research discoveries to market to help address grand societal challenges such as those in sustainability and healthcare. The project will also have impact beyond the local workforce, by implementing, assessing, and disseminating a successful curriculum for training students in team-based research focused on emergent intelligence. The NSF Research Traineeship (NRT) Program is designed to encourage the development and implementation of bold, new potentially transformative models for STEM graduate education training. The program is dedicated to effective training of STEM graduate students in high priority interdisciplinary or convergent research areas through comprehensive traineeship models that are innovative, evidence-based, and aligned with changing workforce and research needs. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2024 · 2024-09

Informed consent is a cornerstone of research ethics. However, standard consent procedures often fail to ensure participants understand the content and consequences of their participation in research. This project will extend scientific understanding of informed consent in the social and behavioral sciences by probing participant comprehension of data sharing options and preferences for confidentiality. These issue areas have grown in importance as researchers aim to conduct work that is both ethical and transparent. This project involves three related activities. First, the development of a scoping review of past research on the topic. Second, an expert workshop to discuss current practices that aim to enhance ethical consent and research trade-offs in consent design decisions. And third, the collection of original data through focus groups with researchers who seek to obtain consent for surveys, as well as interviews with research participants. Findings from this project will inform researcher decision-making with respect to informed consent design choices and contribute to evidence-based recommendations about how to improve standard practices for obtaining consent. Participation in research is essential for the progress of the social and behavioral sciences, and ensuring genuinely informed consent is key to the ethical treatment of participants. This project seeks to advance scientific understanding of informed consent, focusing on two key issues. First, the project assesses how participants understand confidentiality and data sharing in the informed consent process. Second, it evaluates how participants behave when introduced to various types of content included in the consent script and different modes of obtaining consent. The project begins with a scoping review of prior research on this topic and convening a workshop of experts to identify which issues are most pressing. These activities will inform subsequent original data collection in the United States and abroad. Focus groups will collect enumerator perspectives and recommendations on informed consent processes and gather specific feedback on the informed consent scripts used in cognitive probing interviews. The cognitive interviews will examine how research participants understand and react to content, language, or delivery variations in the informed consent process. This project is funded through the ER2 program by the Directorate for Social, Behavioral and Economic Sciences. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NIH Research Projects · FY 2024 · 2024-08

Racial disparities among older adults in diabetes, cardiovascular disease (CVD), and mortality have widened, in part due to economic recessions such as the Great Recession (2008-2009). The Great Recession disproportionately worsened employment disruptions including precarious employment, health, and survival for Black relative to White workers. Population health research on employment-related health consequences of the Great Recession however do not address vulnerability of prior exposure to precarious employment, leaving a knowledge gap regarding the extent to which precarity during an economic recession maybe superimposed on prior work precarity. This cumulative precarity could exacerbate health disparities for older workers. Economic recessions also deteriorate psychosocial working conditions among those who remain employed. It, however, remains unclear how psychosocial work conditions such as job strain during an economic recession, influence health and mortality when they occur together with cumulative precarity. The objective of this project, therefore, is to assess how pre-recession and successive Great Recession precarity cumulatively shaped employment and work conditions for older Black and White workers, and along with psychosocial working conditions impacted health biomarker trajectories and mortality. I will use 2006-2018 data from the 1) Health and Retirement Study (HRS) and 2) HRS- linked Occupational Information Network Data (O*NET) data to examine the following 3 specific aims: 1) Examine Black-White differences in the independent and co-occurring effects of pre-recession (2006) and Great Recession (2008-2010) precarity on trajectories (2012-2018) of diabetes and CVD biomarkers (hbA1c, cholesterol, C-reactive protein, and systolic blood pressure) and all-cause mortality, 2) Among those who remain employed during the Great Recession, examine Black-White differences in the association of psychosocial work conditions (job strain) with trajectories of diabetes and CVD biomarkers and all-cause mortality, while accounting for cumulative precarity, and 3) Examine whether gender moderates associations observed in Aims 1 and 2. This project is timely, and provides an opportunity to explore and understand these issues as the remnants of the COVID-19 economic recession persist, with additional and disproportionate insults on both employment and health in Blacks, the full extent of which will not be fully elucidated for years to come. An understanding of these associations is important to inform appropriate policies aimed at building social and health safety nets for older workers approaching and preparing for retirement.

NSF Awards · FY 2024 · 2024-08

Public officials can experience significant "backlash,” such as harassment, intimidation, and threats of violence, in response to policies that they develop and implement. Among the outcomes of backlash documented in this research are an inability to function effectively and high levels of personnel turnover. This project analyzes a case in which backlash was not uniform across or within states to identify the conditions under which it arose, its nature and impact and how public officials responded. Answers to these questions contribute to the social science of crisis management and to the development of policies as we prepare for future epidemics or other potentially consequential population health threats. Grounded in social science literature on institutional crisis response and backlash as social and political phenomena, this project develops a unique conceptual framework suggesting hypotheses to account for variation in the experience of crisis and backlash. To evaluate these hypotheses the project uses multiple sources of data: 150-200 key informant interviews with state and local health officials from all US states and two territories (these will be made available to researchers in a digital archive); a data set of social media posts from state legislators and governors; protest data from the Armed Conflict Location and Event Data Project and the Threats and Harassment Dataset. Using these qualitative and quantitative data sets, the project takes a case-comparative methodological approach with several goals in mind: 1) to evaluate and refine the initial conceptual framework; 2) to test the project's initial hypotheses and suggest additional/new ones; 3) to identify in as much detail as possible lessons for public health officials and other authorities as they plan for the next major epidemic. This research is co-funded by the Science of Science: Discovery, Communications, and Impact and the Security and Preparedness Programs. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2024 · 2024-08

This award supports the design of an Open Control and Analysis Architecture for Cosmic Explorer, the concept for a next-generation gravitational-wave observatory in the U.S. Cosmic Explorer will push the reach of gravitational-wave astronomy to the edge of the observable universe, enabling transformative discoveries across physics, astronomy, and cosmology. The Open Control and Analysis Architecture is a critical system that sits between the hardware sensing gravitational waves and the scientific output of the detector. The design of Cosmic Explorer’s digital systems will drive advancements in technologies relevant to other fields of science and industry, including control systems for large-scale experiments; architectures for large-scale scientific computing; and investigation, adoption, and improvement of open-source and industrial hardware and software systems. This award will help recruit and train students and professionals who will become members of the U.S. STEM workforce. Cosmic Explorer will deliver new discoveries, dramatically increase the number of observations, and begin the era of precision gravitational-wave science. The Open Control and Analysis Architecture will be responsible for running the high-bandwidth, high-performance control loops that keep the detectors operating, synchronizing the detector as part of a global network with exquisite timing precision, translating the measured electrical signals into to various kinds of astrophysically relevant outputs, and allowing human insight and control into the detector’s operation and performance. Two key aspects of the proposed design are to make the architecture integrated so that astrophysics is integrated with the operation of the detector and open so that the scientific community can contribute to and extend Cosmic Explorer's science goals. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NIH Research Projects · FY 2025 · 2024-08

Summary Osteocytes are the most numerous cell in bone tissue, which act as mechanosensors and coordinate adaptive bone remodeling. Current model systems have been unable to unify the mechanisms by which osteocytes to sense mechanical stimuli, transmit signals across an extensive 3D network, and how these transient signals drive adaptive bone remodeling by osteoblasts and osteoclasts. In this work, we will use a new bone multicellular unit (BMU) chip that enables longitudinal visualization of mechanosensitive calcium signaling across 3D osteocyte networks, enabling and characterization of the role of this signaling mechanism on the mechanoadaptive response of osteoblasts and osteoclasts in normal and injured states. Using BMU-chip, this work will test the hypothesis, ‘Discontinuity in 3D osteocyte networks alters mechanically-evoked calcium signal propagation which in turn modulates the spatiotemporal remodeling of effector cells’ using three specific aims. Aim 1 will define how Pulsed Unidirectional Fluid Flow Stimuli (PUFFS) modulates dynamic changes in calcium signaling across 3D network of osteocytes. Aim 2 will determine how 3D osteocyte networks subjected to PUFFS modulate direct and indirect signaling and osteoblastic bone formation and osteoclastic resorption activities. Aim 3 will identify how targeted disruption of 3D osteocyte networks influence calcium signaling and long-term functional outcomes. Completion of the proposed aims will provide a comprehensive understanding of how mechanically evoked calcium signaling across osteocyte networks modulates functional outcomes within the BMU in normal and injured conditions. Our team, with complementary expertise in biomedical engineering, bone cell biology, orthopedic surgery and statistical analysis is well suited to execute this project. In the future, BMU- chips could be utilized to probe other mechanotransduction pathways, and accelerate the development and evaluation of drugs to treat bone disease.

NSF Awards · FY 2024 · 2024-08

Gravitational waves from binary black holes and neutron star mergers are being detected at an unprecedented rate. Gravitational wave observatories such as the Advanced LIGO detectors in Hanford, Washington, and Livingston, Louisiana continue to grow in sensitivity to signals from astrophysical origin by reducing noise to their fundamental limits. These detectors rely upon the ability to make heavy mirrors absolutely still, so when a very small gravitational wave passes through the detector, the extremely small relative motion imparted onto the mirrors by the gravitational wave is detectable. Current limitations to the sensitivity to gravitational waves depend significantly on the mass of the mirrors, including quantum radiation pressure noise and noise from the detector controllers pushing on the mirrors. One simple way to increase sensitivity to gravitational waves is to increase the mass of the mirrors. The team will train students in STEM research areas. This award supports the design of a LIGO upgrade to increase suspended test masses from 40 kg to 100 kg. In particular, the PI's team will contribute to the design of the enhanced actuation and calibration systems to accommodate the increased mass of the mirrors while taking full advantage of the sensitivity increases. This work will investigate the performance of the current 40 kg test mass suspensions, both in low-noise and lock acquisition configurations, which will inform simulations and designs of the 100 kg suspensions. The group will also investigate the feasibility of novel actuation schemes, including the possibility of remote test mass control using a high-power auxiliary laser upgrade to the photon calibrator, known as the photon actuator. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2024 · 2024-08

A triple quadrupole ICP-MS will be installed to support research, teaching, and outreach activities at the Department of Earth and Environmental Sciences at Syracuse University. This instrument will have a wide range of users with diverse backgrounds, including those in hydrogeology, paleoenvironmental studies, and solid earth processes. The acquisition of this new instrument will benefit all levels of education at multiple institutions, as well as provide opportunities for public outreach. Student-led undergraduate research using this instrument through several undergraduate STEM-focused training programs at Syracuse University will be promoted. Use of this instrument will highlight this instrument as an example of state-of-the-art analytical work in Earth Sciences when interacting with underrepresented groups. Syracuse K-12 students will have opportunities to tour the ICP-MS laboratory. The instrument capabilities will be showcased through videos broadly disseminated. The ICP-MS instrument measures carbonate iodine to calcium ratios for investigating changes in ocean oxygen patterns through geologic history. These changes recorded in global oceans reflect important environmental changes in the atmosphere, on land and during the evolution of life. Data generated from analyzing samples with this instrument will be compared to Earth system model results and will help constraint future models. The PIs will further develop halogens as hydrogeochemical tracers for both groundwater and surface water applications. The partitioning of iodine between environmentally important minerals (e.g. carbonate and apatite) and aqueous solutions will also be examined. This ICP-MS will be integrated into all levels of established curriculum, which will reach students from lower and upper division undergraduates to graduate students both in person and online. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2024 · 2024-08

Tissues in the body can be compressed or stretched by external and internal mechanical forces, such as the swelling of a region of tissue in contact with another. Abnormally large mechanical forces can lead to significant buildup of stress in the tissue that can damage individual cells and alter their gene expression to perhaps lead to abnormalities in function. However, when a cell is compressed, causing its cell nucleus to compress, nuclear blebs, or protrusions of the nucleoskeletal shell surrounding the genetic material, may form. These blebs can potentially relieve stress build up in the cell nucleus so that it can continue to function normally. Such blebs can even rupture to further relieve stress. The ability of cells, whether individually or in groups, to handle such forces while also maintaining their functionality is known as mechanical homeostasis. Understanding how these physical forces transmit between and within cells and how cells respond and adapt to these forces over time is key to understanding this functional robustness. And yet, due to the interactions at the cell nuclear scale, the cell scale, and the tissue scale, the process is complex, which, up to now, has limited our understanding. To address the multi-tiered chain of complexity underlying mechanical homeostasis, in this award the PIs will build on their prior work at the cell nuclear scale, the cell scale, and the tissue scale to create a comprehensive, multi-tiered physics framework based on experiments and computational models to predict how cell nuclei maintain function under extreme mechanical stress. Specifically, the PIs will focus on how cell compression deforms and damages the nucleus and triggers adaptation mechanisms in the nuceloskeletal shell, such the rehealing of the shell after blebbing and rupture. They will also investigate how whole-cell compression impacts how the genetic material inside the nucleus re-organizes and adapts. Finally, the PIs will explore how tissue-level forces influence chromatin organization and identify new adaptation strategies. With this exploration, the proposal aims to create a universal physics model to explain how cells and tissues adapt to mechanical forces, thereby contributing to the fields of quantitative biology and mechanobiology through the lens of physics. The PIs will also work to promote interdisciplinary education at the university level. Collaborating with creative writing professors at Syracuse University, the project will involve biophysics undergraduates and creative writing students in joint activities. This will include lectures on biophysics in creative writing classes, lectures on writing in biophysics courses, and collaborative writing projects. This initiative aims to improve communication skills, foster creativity, and break down barriers between the disciplines. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NIH Research Projects · FY 2025 · 2024-08

PROJECT SUMMARY / ABSTRACT Disruptions in neuronal development and connectivity within the neocortex, the area of the brain responsible for high cognitive function, are found in many neurodevelopmental disorders (NDDs), including autism spectrum disorders, intellectual disability, and schizophrenia. What causes this atypical development is still poorly understood, but likely includes a combination of genetic, epigenetic, and environmental factors, including maternal nutrition. We thus propose to study how genetic, epigenetic, and maternal nutrition factors intersect to regulate two major developmental convergence points for NDDs: the proliferation and differentiation of neuronal progenitors, and the establishment of appropriate local and long-distance neuronal connections. To investigate these mechanisms, we will employ Cited2 forebrain-specific conditional knockout (cKO) mice, which our previous work demonstrated have disruptions in these conversion points of neocortical development, and display behavioral abnormalities associated with human NDDs. CITED2 is a transcriptional co-regulator that recruits the histone acetyltransferase complex CBP/p300, thus Cited2 loss-of-function (LOF) leads to disruptions in the epigenome and alterations in the transcriptome. Importantly, maternal folic acid supplementation rescues neural tube closure defects in Cited2-null embryos; whether it also modifies neocortical phenotypes is unknown although maternal folic acid supplementation in humans is associated with reduced risk of NDDs. We hypothesize that maternal folic acid supplementation will rescue the atypical neocortical development and behavior in Cited2 cKO mice. We propose to test this hypothesis by examining regulation of progenitor proliferation and differentiation, precise axonal connectivity, and behavior in Cited2 cKO and wildtype littermates, with sufficient vs. supplemented maternal folic acid diets (Aim 1). Folic acid is a methyl donor and alters DNA methylation, an important epigenetic modification associated with gene silencing. Thus, to determine whether the alteration of neocortical development with folic acid occurs due to modification of gene regulatory networks disrupted with Cited2 LOF directly, or whether compensatory pathways are modified, we propose to employ antibody-based fluorescence activated cell sorting to purify Cited2 cKO and wildtype neocortical intermediate progenitor cells (IPCs) at E15.5, with both sufficient and supplemented maternal FA, and perform RNA-seq and Methyl-seq (Aim 2). Together, these approaches have the potential to identify entirely novel genes and pathways underpinning gene x environment interactions controlling neocortical development, and to open new avenues for investigation.

NSF Awards · FY 2024 · 2024-08

As a mathematician faced with a research problem or an educational task, the PI strives to abstract away inessential information, break down complicated structures into simple components, and identify the right tools for the job. In this project, the PI plans to apply methods from disparate fields such as discrete mathematics and homotopy theory to problems in geometry, especially problems involving the impact of symmetry and local curvature conditions on the global shape of high-dimensional objects called manifolds. Crucial to this progress are communication and collaboration with experts from across the country and around the globe whose areas of expertise both overlap and supplement the PI’s. Additional aspects of this project include growing and diversifying the body of students, researchers, and experts in STEM fields who will positively impact the advancement of the research goals of this project, the future of STEM education, and our society’s ability more broadly to tackle difficult scientific problems. The PI will analyze local-to-global principles in geometry. Goals involve analyzing the interaction of (local) positive curvature conditions in Riemannian geometry and (global) algebraic topological and symmetric structures. The PI will apply tools from homotopy theory, equivariant cohomology theory, matroid theory, and topological graph theory. These methods have applications in the Grove Symmetry Program but do not use curvature, so this work has the potential to apply in other areas of geometry. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2024 · 2024-08

The U.S. lacks resources for many minerals that contain elements critical to the national economy and to national security. This project will explore new sources of the chemical elements called the “rare earth elements” (REEs). These are metallic elements with strong magnetic properties and are critical to the energy transition. There is only one currently producing domestic U.S. source of REE. The majority of world production of REEs is from a single mine in China. The proposed research will explore for REE mineral deposits in bedrock, stream sediments, and sedimentary rocks in the Piedmont and Coastal Plain provinces. The mineral monazite is the most common REE-bearing mineral in the crust. Preliminary research demonstrated that monazite is widespread in the region. This new project will address the following questions. (1) What is the source of the monazite currently transported by rivers from the Appalachian Mountains to the Atlantic coast? (2) Is the source metamorphic rocks or igneous rocks, or both? (3) Has the source changed over geologic time? (4) What are the best methods for locating these deposits? Methods used to answer the questions include mass spectrometry and scanning electron microscopy. The answers will permit mineral exploration companies to focus exploration and development on the highest-grade source regions. The project will train graduate and undergraduate students at the University of Kentucky and Syracuse University. Upon graduation these students will be prepared to join the workforce in critical mineral exploration. The project will involve a high school earth science teacher to create science education content. The research will improve the ability of the U.S. to address the critical mineral needs outlined in Executive Orders 13953 and 14017. Research will test hypotheses for the provenance of detrital monazite in clastic systems in the Atlantic Coastal Plain that were demonstrated by the USGS to be critical REE placer mineral deposits. The research addresses the GEO-CM charge of research “leading to advanced understanding of geologic and geochemical processes through which critical minerals form and are concentrated into economically viable deposits”. The Atlantic Coastal Plain province has proven REE potential based on detrital monazite in Upper Cretaceous to modern clastic systems between the Fall Line and the Atlantic littoral zone. The long-hypothesized source of monazite in these deposits are belts of middle to late Paleozoic medium- to high-grade metapelites and granitic magmatic rocks in the crystalline Piedmont and Blue Ridge Provinces. Rather than using detrital zircon as a proxy for the heavy mineral suite, the researchers will date the ore mineral of interest (monazite) for testing provenance models. High-throughput monazite laser ablation-split stream-inductively coupled plasma-mass spectrometry (LASS-ICP-MS) will be used to obtain U-Pb dates and REE concentrations. They will conduct a geochronologic survey of monazite in potential bedrock metamorphic and magmatic sources, not already characterized by their prior research, which will be used to assess provenance and sediment delivery paths from inferred Appalachian sources to Coastal Plain clastic systems. In addition to monazite age and REE variations, the researchers will measure Nd isotope compositions in detrital monazite and source rocks as additional tests of provenance. Samples will include crystalline bedrock (metamorphic and granitic units), modern sediment in headwater streams and trunk streams flowing to the coast (e.g., the Broad River drainage basin), and Upper Cretaceous to Lower Tertiary coastal plain sediments at the Fall Line that are exceptionally high in detrital monazite. The project will train graduate and undergraduate students at the University of Kentucky and Syracuse University. Upon graduation these students will be prepared to join the workforce in critical mineral exploration. The project will involve a high school earth science teacher to create science education content. The research will improve the ability of the U.S. to address the critical mineral needs outlined in Executive Orders 13953 and 14017. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2024 · 2024-08

This award provides travel funding for US-based participants in the week-long workshop “Betti numbers in commutative algebra and equivariant homotopy theory” to be held September 23–27, 2024, at Bielefeld University, in Bielefeld, Germany. The workshop centers on a series of long-standing conjectures that appear in parallel in two major fields of mathematics. The goal of the workshop is to bring together researchers from these two fields to discuss recent advances on these conjectures. Another goal is to train more researchers to work on these important problems and help them build connections between the two fields. The overarching goal of this award would be to increase US participation in this highly active area of research, and to foster collaborations between US mathematicians and those from other countries. The funding is aimed especially at postdoctoral fellows and graduate students, as well as participants who do not have independent funding, to attend this workshop, and it will also be used to encourage participation by individuals from underrepresented groups in mathematics. A recent workshop held in Banff, Canada in 2022 initiated this goal, and funding for this event would cement the connections already made and build new ones for younger participants. The bridges we are building will not only connect researchers located in different countries but also between those working in different areas of mathematics. Algebra and topology are thriving branches of mathematics that are well represented in most math departments. Commutative algebra, as the algebraic underpinnings of algebraic geometry, and algebraic topology, with its strong focus on homology and homotopy, have occasional significant overlap in both methods and aims. The goal is to create a strong working alliance between the groups working on these conjectures and related problems, and also to get younger researchers involved in these problems. In fact, total Betti numbers appear in related, decades-old rank conjectures in commutative algebra and equivariant topology. On the topological side, Halperin and Carlsson conjectured that the total Betti number of a compact space with a free torus action or p-torus action of rank r is bounded below by 2r, which has inspired much research on the topological side of spaces with a group action. On the algebraic side, Avramov conjectured a similar lower bound for the total Betti number of finite length modules over a local ring. Recent work of Walker and VandeBogert-Walker resolves this conjecture positively for rings of prime characteristic, whereas counterexamples to a stronger conjecture show the subtlety of the questions. The web site for the workshop is at https://www.math.uni-bielefeld.de/birep/meetings/betti2024/index.php and includes a full speaker list. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NIH Research Projects · FY 2025 · 2024-07

PROJECT SUMMARY/ABSTRACT Despite its importance to the continuation of species, the differentiation of primordial germ cells into functional oocytes is poorly understood. Primordial germ cells begin to differentiate into oocytes during embryonic development in the mouse. The oocytes develop in clusters called germline cysts, a conserved phase of oocyte development in both vertebrates and invertebrates. Oocytes progress through prophase I of meiosis and arrest at the diplotene stage. They then undergo primordial follicle formation during which germ cell cysts break apart into single oocytes (cyst breakdown) and granulosa cells migrate around individual oocytes to form primordial follicles. During the process of cyst breakdown, a subset of cells in each cyst die with only a third of the initial number of oocytes surviving to form primordial follicles. The mechanisms that control assembly of primordial follicles are not well understood. The long-term goal is to understand molecular and cellular mechanisms used to establish the primordial follicle pool in the mouse ovary. Published work from the applicant’s lab using ovary organ culture suggests that signaling through the receptor tyrosine kinase, KIT, promotes the assembly of primordial follicles. In addition, preliminary data suggest that KIT can signal through the phosphoinositide 3-kinase (PI3K) pathway to promotes primordial follicle formation but that other signals besides KIT such as insulin may be important. The objective of this proposal is to understand the role to understand the role of insulin in primordial follicle formation. The central hypothesis of the proposed research is that in addition to KIT signaling, insulin signaling promotes primordial follicle assembly through the PI3K signal transduction pathway activating molecules that promote follicle formation and repressing molecules that maintain oocytes in cysts. The specific aims of this research are to: 1) elucidate the role of insulin signaling in primordial follicle formation; and 2) examine primordial follicle formation in a mouse model of gestational diabetes. These goals will be achieved through techniques including immunohistochemistry, confocal microscopy, ovary organ culture, and genetics. Research proposed in the current application is significant because it will enhance current knowledge by elucidating the mechanisms important to establish the primordial follicle pool. Results obtained in this grant will help improve research efforts in ovarian biology and in treatment of conditions causing female infertility such as primary ovarian insufficiency.

NSF Awards · FY 2024 · 2024-07

The high-tech industries of the future need trained workers who are excited about science and technology. Syracuse is a city that is ripe for opportunities, and recent economic developments in the technology sector locally indicate that the city needs a well-trained technological workforce to meet the future demand. The Physics Department at Syracuse University has an epic goal to become a touchstone for historically excluded groups in physics, focusing on Black, Latino, Indigenous, and women students. To achieve that goal, the proposed Syracuse University Physics Emerging Research Technologies Summer High school Internship Program (SUPER-Tech SHIP) will connect students to the exposure, knowledge, and skills they need for the quantum, semiconductor, and biotech opportunities that are growing locally. SUPER-Tech SHIP is a paid summer high school research internship program for students from local area high schools in the city of Syracuse and surrounding areas of Central New York. The program will meet students where they are and invite and welcome them into our research community to help them see themselves in these roles. The SUPER-Tech SHIP program is an essential component for facilitating students’ first step from high school into technological careers through direct exposure to several emergent technology fields. The Syracuse area has a rapidly expanding industrial footprint for these emerging fields, and these high-tech sectors will need a workforce that understands technology. Syracuse Physics is uniquely positioned to build a diverse workforce for emerging technologies because our region has a high population of historically excluded groups, there is an outstanding research university with excellent scientists working in emerging technological fields, there is a wonderful town-gown relationship, and there are local industries and research labs in need of many technical workers. Leveraging all this, SUPER-Tech SHIP will create the pipeline for a diverse future workforce to the benefit of the industries and the local community. This is an ExLENT Explorations proposal to expose high school students to the skills and concepts of emerging technology fields found in the Syracuse University Physics Department including: quantum information, semiconductors, and biotechnology. This project is a major partnership with Syracuse City School District (SCSD), an inner-city district with high numbers of students from groups historically excluded from physics. The new program, SUPER-Tech SHIP, will have the following elements (1) recruitment by Syracuse Physics faculty visiting all Syracuse City School District science classrooms, (2) an application process focused on student persistence, (3) initial bootcamps to orient and ready the students for all the internships in research labs, (4) a longer-term research experience in a lab, and (5) an end of the program poster session and celebration with friends, family, and teachers. The SUPER-Tech SHIP will include bringing back prior participants to serve as near-peer mentors to the high school participants. New partners from industry and national labs are being incorporated to give more role-models with whom student participants will network. Extensive cohort building, assertive mentoring, and belonging interventions will be implemented through the SUPER-Tech SHIP. In labs, participants will work in pairs to have a local peer mentor. Student pairs will mix during orientation bootcamps to expand their peer network. Near-peer mentors (undergrads and prior cohort participants) will be involved in research with the participants. Weekly fun activities will explore the campus to acclimate high school participants. Within the Syracuse Physics Department, a dedicated space will be created for these students for the duration of the 6-week program. A SCSD teacher will check in with students weekly and give feedback to the department on real-time changes. Students will also have weekly science seminars and lunch with speakers from the faculty, industry, and a local Air Force Research Lab. Finally, the program will have a dedicated graduate student administrative staff member from the same neighborhoods as the high school participants to serve as a resource and mentor. Systemic barriers to internships exist for Syracuse City students. To recruit students and eliminate barriers, the internship provides each student with a significant stipend, daily transportation to and front the university, and daily breakfast and lunch at a dining hall on campus. These mechanisms are needed to (1) entice students to this opportunity, (2) make it worth their while financially compared to other jobs in the summer, (3) reduce barriers of transportation in the city, and (4) increase food security of the students while in our program. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2024 · 2024-07

This project aims to serve the national interest by improving physics education across the country by increasing faculty uptake of computational physics topics in undergraduate courses. Computational skills are crucial in all areas of science and engineering, and it is important for students to develop these computational skills in the context of their undergraduate physics education. The Partnership for Integration of Computation into Undergraduate Physics (PICUP) has been working for the last several years to build a community of educators to support this mission. This IUSE level 2 Institutional and Community Transformation (ICT) project will leverage the growing PICUP community to establish regional workshops throughout the country that will be sustained in the years to come through local leadership within each region. These regions have been specifically selected in order to maximize PICUP's impact on Minority Serving Institutions (MSIs) and Two Year Colleges (TYCs), with the goal of assisting physics faculty from at least 50% of the nation’s bachelor’s granting physics departments and 25% of TYC departments in their endeavors to integrate computational activities into their physics courses. Alongside the regional faculty-development workshops, the project will build national community through national workshops and leadership development. The project supports research to investigate students' learning in computational physics across a variety of contexts. The research results will drive the development of an assessment framework for student learning of computation in undergraduate physics courses. Instructors from TYCs and other special-focus institutions will be included in the assessment framework research, which will help support the inclusion of students who are historically understudied in physics education research. The NSF IUSE: EDU Program supports research and development projects to improve the effectiveness of STEM education for all students. Through the Institutional and Community Transformation track, the program supports efforts to transform and improve STEM education across institutions of higher education and disciplinary communities. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NIH Research Projects · FY 2026 · 2024-04

PROJECT SUMMARY/ABSTRACT Our understanding of human intestinal development is limited by a lack of tissue accessibility and limitations to existing benchtop models. These laboratory models have advanced with the emergence of organoids, which can better recapitulate the cellular composition and spatial organization of tissue-specific cells than classical in vitro models. Further, induced pluripotent stem cell (iPSC)-derived intestinal organoids (HIOs) are particularly relevant in modeling human intestinal development. However, state-of-the-art protocols fail to account for all relevant niche cues that may influence cell fate, maturation, and morphogenesis, yielding organoids with an immature (i.e., fetal-like) gene signature that limits their relevancy in modeling human disease. Crucially, the timing of exposure to niche cues is vital for proper fate specification. Additionally, we hypothesize that niche cues, beyond the traditionally studied soluble biochemical factors, namely the dynamic properties of the surrounding extracellular matrix (ECM), can and will alter cell signaling and subsequent changes to cell fate. We propose to use a reductionist approach to study the role of the ECM on HIO-derived epithelial organoids (HDEs) and design “blank-slate” biomaterials to precisely and specifically match the properties of the niche that are amenable to organoid growth, then globally and locally alter these properties to understand their role in cell fate decisions, maturation state, and the generation of biomimetic intestinal crypt-villus architecture. We posit that by using advanced imaging techniques, including expansion microscopy and metabolic labeling of nascent proteins, we will be able to further characterize how the ECM changes globally and locally as HDEs grow. In Aim 1, we will investigate how phototunable changes to matrix stiffness (by controlled softening or stiffening) change HDE cellular composition and maturation state over time. In Aim 2, we will spatiotemporally alter local matrix mechanics by photoinduced matrix softening to coax architectural changes to growing HDEs to match in vivo crypt dimensions. We will then study how these changes influence cell fate and maturation. In the K99 phase of the award, Prof. Kristi Anseth, a luminary in using dynamic PEG-based hydrogel materials for manipulating cellular phenotypes, and Prof. Peter Dempsey, a world-leading expert in intestinal biology, will serve as my co- mentors. I will consult my mentoring team, including Prof. Jason Spence (iPSC-derived organoids, scRNA-seq), Prof. Richard Benninger (imaging and image analysis), Dr. Joseph Dragavon (imaging and image analysis), and Prof. Jay Hesselberth (scRNA-seq and bioinformatics analysis). My K99 training will consist of learning key iPSC- derived organoid techniques, advanced imaging and image analysis methods, and scRNA-seq analysis and interpretation to propel me towards developing better models of human development to understand the role ECM niche cues during the independent investigator R00 phase. In sum, the proposed research will address an unmet need to specifically study the role of the ECM in intestinal development and controllably tune properties of the ECM to build better models of the intestine towards improved translational efficacy in future studies.

NIH Research Projects · FY 2025 · 2023-09

Project Summary Developing novel technologies for identifying and quantifying transient protein-protein interactions is critical in basic research and medical biotechnology. Protein kinases represent a focal group among strategic drug targets for treating numerous hematological malignancies and solid tumors. Yet, creating high-resolution sensors to detect, quantify, and analyze the plasticity of diverse kinome members in a broad dynamic range of interactions remains difficult. This challenge is exacerbated because the kinase superfamily members vary drastically in their complexity. To address this long-standing technological shortcoming, we will formulate, develop, and validate a new class of generalizable and highly specific nanopore sensors (nanosensors) for kinase analytics. The key innovating aspect of this design is fusing a generic protein recognition ligand with a transmembrane protein nanopore. This approach will employ a robust nanostructure made of a single polypeptide entity with no requirement for an additional tail or other exogenous tags. The binding interface of the protein recognition ligand is interchangeable to accommodate the required specificity for a targeted kinase, whereas the nanopore facilitates the generation of a reporting electrical signal. A protein kinase analyte in solution produces a unique electrical signature that varies with its identity and quantity. The reporting signal is mediated by the ligand-kinase assembly at the nanopore tip. In these studies, kinase recognition events will be discriminated at single-molecule precision without the necessity of using complex data analysis algorithms. This engineering strategy substantially broadens the spectrum of applications of these nanosensors to various kinases and their interactions. Our preliminary studies prove the power of this approach by creating a single- molecule nanosensor platform that probes and quantifies structurally and functionally diverse proteins beyond the fundamental limit of sensing inside the nanopore. In addition, such a tactic will enable the detection of competing binding interactions of kinase isoforms against the same recognition ligand. These generalizable nanosensors permit integration into scalable devices, representing versatile elements for small-molecule inhibitor screening and drug discovery pipelines. Further project developments will be aimed at maintaining a high performance of these nanosensors in a complex biofluid. Therefore, they can be utilized using realistic samples, having prospects in molecular diagnostics. The expected immediate outcomes of this project will be the following: (i) the development of high-affinity nanosensors for ultrasensitive analysis of receptor tyrosine kinases (RTKs); (ii) the creation of genetically-encoded nanosensors for probing serine-threonine kinases (STKs); (iii) the detection and analysis of kinases in multiplexed settings and biofluids. These studies will impact healthcare by providing tools and a fundamental framework in biosensor technology, synthetic biology, and single-molecule enzymology.

NIH Research Projects · FY 2025 · 2023-09

Project Summary/Abstract Alcohol consumption at hazardous levels is associated with negative consequences at nearly every step of the HIV care continuum. It is a critical factor in HIV treatment that significantly contributes to poor treatment-related outcomes. Randomized clinical trials (RCTs) of alcohol interventions for people with HIV (PWH) have had limited success, perhaps due to an increasingly recognized syndemic of co-occurring hazardous alcohol use and other mental health-related problems among PWH. Up to 63% of PWH meet criteria for both a substance use disorder and another psychiatric disorder—necessitating a shift in the literature towards transdiagnostic approaches that target core psychological processes that underlie multiple mental health and substance- related problems. One transdiagnostic mechanism that is particularly relevant to alcohol and other substance use is experiential avoidance (EA)— i.e., repeated, and maladaptive, use of substances and/or other behaviors to escape or avoid unwanted thoughts, feelings, and/or urges. Acceptance and commitment therapy (ACT) is a promising transdiagnostic intervention for PWH that targets EA. ACT is an empirically supported treatment for multiple psychological and behavioral health-related outcomes; however there have not been any full-scale RCTs of ACT for alcohol use among any population, including PWH. We recently adapted a telephone- delivered ACT intervention originally developed for smoking cessation, into an intervention for PWH who drink at hazardous levels (NIH/NIAAA; R34AA026246). With a multidisciplinary team, and with two rounds of input from PWH, we developed a six-session, telephone-delivered ACT intervention for alcohol use and subsequently conducted a pilot feasibility/acceptability RCT. We found high acceptability of the adapted ACT intervention, and evidence of feasibility for conducting a full-scale, remote, RCT. The overall objective of this application is therefore to determine the relative efficacy of ACT, compared to a standard Brief Alcohol Intervention (BI), for reducing alcohol use and comorbid symptoms of depression, anxiety, and stress among adult PWH who are hazardous drinkers. The specific aims are: To determine the relative efficacy of ACT, compared to BI, for reducing alcohol use among PWH (Aim 1) and to determine if ACT has an effect on transdiagnostic processes that in turn affect alcohol use and other psychological and functional outcomes (Aim 2). We will accomplish these aims by: conducting a fully remote, relative efficacy RCT in which we randomly assign 300 PWH who are hazardous drinkers to either the ACT intervention we developed (n = 150), or a BI intervention (n = 150) previously shown to reduce alcohol use among PWH. We will assess alcohol-related outcomes—via self-report and a biomarker (phosphatidylethanol) – at baseline, post-treatment, and again 3-, 6-, and 12-months post-randomization. We will also measure EA to determine if it mediates treatment effects for alcohol use and other psychological (i.e., symptoms of depression, anxiety, and stress) and functional outcomes, measured at all timepoints.

NIH Research Projects · FY 2024 · 2023-08

Summary/Abstract Young adulthood is a developmental epoch for alcohol misuse (defined as a pattern of drinking that increases risks for adverse health outcomes). Multiracial (defined as having biological parents of two or more racial/ethnic groups) young adults may be differentially vulnerable to alcohol misuse as they report both the highest prevalence of past-year alcohol consumption and alcohol use disorder compared to other racial/ethnic young adults. Multiracial discrimination is a racially relevant stressor for Multiracial young adults and may be associated with alcohol-related disparities, as consistent with minority stress and tension reduction frameworks, as well as robust support for the discrimination-alcohol misuse association in monoracial young adults. However, our knowledge of Multiracial discrimination is fragmented and compounded by measurement concerns. Notably, general discrimination scales are commonly used to assess Multiracial discrimination despite research demonstrating general discrimination and Multiracial discrimination as distinct constructs. Further, existing Multiracial discrimination scales lack specificity with the source of the discriminatory treatment even though discriminatory messages vary by perpetrators and may be differentially associated with health (including alcohol) outcomes. In the absence of a scale capturing the lived experience of Multiracial discrimination among Multiracial people, alcohol researchers cannot resolve whether Multiracial discrimination is a sociocultural determinant of alcohol misuse and contributing to alcohol-related disparities among Multiracial young adults, who are driving substantial demographic change in the United States. Thus, using a sequential mixed methods approach, the proposed project aims to (a) explore and generate a nuanced view of Multiracial discrimination using thematic analysis from Multiracial young adult focus groups, (b) develop and (c) psychometrically validate the Multiracial Discrimination Scale using exploratory and confirmatory factor analyses, and (d) assess concurrent associations between Multiracial discrimination with alcohol misuse using structural equational modeling. Findings of this project will provide alcohol researchers with a psychometrically sound scale to characterize the scope and magnitude of the Multiracial discrimination-alcohol misuse pathway, to potentially highlight an intervention point preceding alcohol misuse, and thus informing the culturally sensitive design of evidence-based interventions implemented to reduce and prevent alcohol misuse among Multiracial young adults. This NRSA Individual Predoctoral Fellowship to Promote Diversity in Health-Related Research would provide specialized training in mixed methodologies (e.g., connecting qualitative/quantitative data), psychometric statistics (e.g., test theory), and investigating latent constructs (e.g., structural equation modeling), thus providing instrumental support for my developing research program, and laying out a path for a long, prolific, NIH-funded alcohol research career.

NIH Research Projects · FY 2025 · 2023-08

Project summary/abstract Decisions an animal makes on the basis of multi-sensory input are crucial to its survival. How do neural circuits resolve conflicts to choose among available behaviors while receiving multiple and variable inputs? The navigational behaviors of larval Drosophila form a promising model in which to relate neural activity and behavior. Powerful genetic reagents are available in Drosophila to target nearly arbitrary subsets of 10,000 neurons that make up the larva’s central nervous system (~3, 000 in the brain hemispheres), and an EM reconstruction of this network is almost complete. The larva’s cuticle is semi-transparent, and the entirety of its representative insect brain is optically accessible for in vivo interrogation or manipulation. Even a simple organism like the larva responds variably to seemingly identical stimulus presentations. What is the origin of this variability? This question can be phrased using the language of information theory. If I repeatedly present the same stimulus and observe different behaviors, then the stimulus does not contain full information about the behavior. But directly measuring the activities of the motor neurons that control movement would always allow one to predict the behavior; these neurons have more informationabout the behavior than is present in the stimulus, and this extra information originates somewhere in the nervous system. The task of finding where and how variability originates in larva’s tractable nervous system requires an integrated approach in describing a behavior, identifying which neurons are involved, resolving how circuit activity encodes those behaviors, and discovering the mechanisms generating these neural transformations. To achieve this task, I have developed two techniques of neural circuit interrogation: an optogenetic reverse-correlation behavioral assay that can determine the role of any targeted neuron in decision making, and a first ever two-photon tracking microscope that can record the neural activity as larva freely navigates its sensory environments. In this project, I will decode the circuitry underlying the larva’s navigational responses to uni- and multi-sensory input. In many neurological and psychiatric disorders, such as schizophrenia, autism spectrum disorder, dyslexia, and ADHD, the processing of multisensory information is compromised, perhaps from abnormalities in the neural circuits that are responsible for integrating sensory information. This research will advance our understanding of the neural basis of multisensory decision-making, which will allow us to better understand the defects in information processing that occur during disease.

NIH Research Projects · FY 2025 · 2023-08

PROJECT SUMMARY/ABSTRACT In this MIRA program, we aim to gain atomic-level insights into complex biological systems such as bacterial membrane proteins and light-sensitive proteins with particular emphasis on their native protein and lipid environments. We will test the impact of such biochemical environments in two distinct projects. A wide variety of toxic chemicals, including toxic metal oxides and hydroxides, pollute our environment, posing an imminent threat to human life. One can leverage the unique respiration mechanism in marine microbes like Shewanella to revolutionize bioremediation and wastewater treatment technology. Molecular modeling and computations will provide an atomic-scale comprehension of the mechanism that will augment macroscale experimental observables. In the first project, we will model the outer membrane cytochrome-porin complex of Shewanella oneidensis in its native environment and obtain molecular insights into the charge-transfer network employed in its respiration. Electronically excited-state processes are ubiquitous in nature and biotechnology. For example, blue-light-sensitive proteins are used in the optogenetic control of cellular processes. Fluorescent proteins with emissions spanning the entire visible region are often utilized for in vivo imaging. In these applications, subtle structural changes in an electronically excited molecule induce pronounced conformational changes in the nearby protein environment or further from its location (allostery). Therefore, the biochemical environment relays the information at the photon-absorption site to another site. Most conformational changes occur well beyond a few nanoseconds, making them inaccessible to modern multi-scale quantum mechanics/molecular mechanics (QM/MM) techniques. Therefore, in the second project, we will build a tool to model excited states of biomolecules using force field parameters and then validate those parameters using a few case studies with fluorescent proteins. Furthermore, we will use those parameters to decipher photoinduced allosteric pathways in blue-light-sensitive proteins.