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Michigan Arts and Culture Council

The Michigan Arts and Culture Council awards grants to arts organizations, artists, schools, and communities to support arts education, cultural programming, and creative sector development across Michigan.

Michigan Council on the Arts

General operating support grants for arts organizations in Michigan. Funded by the National Endowment for the Arts and state appropriations.

Michigan Council on the Arts

Project-based grants for arts programming, performances, exhibitions, and community engagement in Michigan.

Michigan Council for Arts & Cultural Affairs

Michigan Council for Arts & Cultural Affairs provides grants to support arts and cultural programming, artist fellowships, arts education, and community-based arts projects across MI.

Mid Atlantic Arts

Project and operating grants for arts organizations and individual artists from Mid Atlantic Arts. Supports visual, performing, literary, and media arts.

Mid Atlantic Arts

Regional arts grants supporting touring performances, exhibitions, and cultural exchange. Mid Atlantic Arts serves multiple states with NEA-funded programs for arts organizations.

Mid-America Arts Alliance

Project and operating grants for arts organizations and individual artists from Mid-America Arts Alliance. Supports visual, performing, literary, and media arts.

Mid-America Arts Alliance

Regional arts grants supporting touring performances, exhibitions, and cultural exchange. Mid-America Arts Alliance serves multiple states with NEA-funded programs for arts organizations.

NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases

Project Summary Type 2 diabetes mellitus (T2DM) is a chronic condition characterized by impaired blood glucose control ultimately leading to cardiovascular, renal, and cognitive dysfunction. T2DM prevalence continues to rise in the U.S., with massive health and financial consequences. Current diet and exercise recommendations often fall short in helping adults with T2DM achieve long-term glycemic control because they inadequately address common psychological barriers (such as chronic stress) that undermine adherence to lifestyle behavior change. Mindful eating and yoga have emerged as promising strategies for T2DM management by combining mindfulness practice with physical activity, dietary habits, and diabetes self-management. Both mindful eating and yoga have independently shown promise for improving glycemic control in adults with T2DM. Mindful eating may help improve emotional regulation, strengthen awareness of internal hunger and satiety cues, and promote increased consumption of nutrient-dense foods, all of which can contribute to improved blood glucose management. Similarly, yoga has shown promise for reducing stress, reducing inflammation, and indirectly supporting T2DM management by fostering healthier attitudes toward lifestyle changes. However, current research has several limitations, including a limited understanding of the mechanisms driving these effects, inconsistent use of yoga types across studies, a scarcity of studies conducted in the U.S, and few studies assessing the combined impact of mindful eating and mindful movement for adults with T2DM. Therefore, rigorous and culturally diverse research is needed to evaluate the combined impact of mindful eating and yoga on T2DM management. We propose a 12-week pilot randomized controlled trial (RCT) to assess the feasibility, acceptability, and early efficacy of a combined mindful eating and yoga intervention to lay the groundwork for a larger efficacy trial. Using a single-blind, two arm RCT, 60 adults (>18 years old) will be assigned to either: a mindful eating and mindful movement group (MEMO) or a standard of care exercise and diet group aligned with American Diabetes Association recommendations. Both groups will engage in hour-long exercise sessions 3x/week and group diet counseling sessions 1x/week. As the primary outcome, a comprehensive battery of feasibility and acceptability measures will be used to determine if a combined mindful eating and yoga program can be successfully delivered to this population. To quantify the impact of mindfulness on key health and clinical outcomes, we will use state-of-the-art measures, including biomarkers (cortisol and HgbA1c), accelerometer-measured physical activity levels, validated dietary assessments, and psychological health scales. Although this pilot study is not designed to establish definitive effects, these measures will provide valuable preliminary insights into how mindfulness delivered via mindful eating practices and yoga may influence metabolic, behavioral, and psychological outcomes in T2DM.

NIGMS - National Institute of General Medical Sciences

PROJECT SUMMARY This application seeks funds to purchase a MINFLUX 3D Microscope. This instrument would support nine NIH-funded users in five departments and four colleges within the Texas A&M University (TAMU) community and a group of four NIH-funded investigators at UT Southwestern Medical Center. The MINFLUX microscope would be the second major instrument in a recently established shared user facility, the Joint Microscopy Laboratory (JML), which is focused on single molecule fluorescence applications. The JML includes significant wet-lab and tissue culture space to encourage use by more distant laboratories both on campus and external to the university. MINFLUX is a relatively new state-of-the-art pointillistic imaging and particle tracking strategy that is extremely thrifty with the use of photons, requiring ~10-fold less photons than the common PALM/STORM- type pointillistic super-resolution approaches. Consequently, MINFLUX can achieve precision levels of a few nanometers on a sub-millisecond timescale within functionally active cellular systems and long single molecule trajectories in three-dimensions (3D) can be obtained using single fluorophore tags. The requested MINFLUX 3D system will enable numerous multi-color strategies combining both static imaging and molecular tracking approaches. Users will examine well-controlled in vitro systems as well as stabilized and complex cellular systems (fixed and permeabilized cells), many with an eye towards live cell investigations. The Major Users will examine fundamental and diverse cell biological and mechanistic biochemistry questions focused on nucleocytoplasmic transport, condensates, bacterial pili, nuclear mechanical stress and synapses. The Minor Users projects include structure, function and biophysical studies of mitochondrial RNA editing and kinase signaling, chemotaxis, endosomal escape, endocytic recycling, antibiotic biosynthesis, phage infection, and additional projects on condensates and synapses. The full-time technician needed to run the MINFLUX microscope will be supported by a combination of user fees and ongoing contributions from departments, colleges, Texas A&M Health, and the Vice President for Research, emphasizing the widespread importance of the new microscope capabilities to advance the capabilities and growth of current research programs. The instrument will be housed in the College of Medicine by the Department of Cell Biology and Genetics, which has donated substantial equipment and space for the nascent JML microscope facility. Altogether, the identified users have planned new research directions that are expected to ultimately require > 90% of the total accessible user time, indicating the substantial demand for both existing and newly developing projects. In total, the requested MINFLUX 3D microscope will provide substantial and fundamental infrastructural support for a wide range of projects important for understanding and improving human health.

Mini Mart City Park

Mini Mart Art Attacks will be held from Sept 2023-April 2024 with curated monthly event series centered around local art, food, and community. All events will be free-of-cost. Each month will include: (1) a gallery exhibit showcasing a local artist, (2) a public art experience or workshop, and (3) a community meal prepared by a local chef. At the end of the series, we will curate a booklet showcasing featured artists, chefs and community members who participated throughout the project. Copies will be available for free to the community.

OD - NIH Office of the Director

Project Summary/Abstract This proposal requests the purchase of the Miniaturized Two-Photon Microscope (Mini-2P) Imaging System from Thorlabs, Inc., a complete state-of-the-art system designed to advance neuroscience research. This lightweight, head-mounted system enables high-resolution, dual-color imaging in freely moving animals, surpassing the limitations of traditional one-photon miniscopes and benchtop two-photon microscopes. It will support immediately five Major Users with NIH-funded projects to explore brain functions, such as reward processing, adult neurogenesis, and social behavior regulation, by providing unprecedented insights into intact neuronal activity. For instance, it will allow simultaneous imaging of distinct neuronal populations in the Nucleus Accumbens during reward tasks and longitudinal tracking of hippocampal neurons during navigation. The Mini-2P will also enhance the Animal Behavior Core, supporting over 20 laboratories at the Albert Einstein College of Medicine. By facilitating studies of brain circuits in naturalistic settings, this instrument will drive discoveries in neurological disorders like addiction and autism, aligning with Einstein’s efforts in advancement of medical knowledge and practice. Institutional support, including funding and expert staffing, ensures its sustainability, fostering collaboration, training, and innovation in neuroscience research.

NIDA - National Institute on Drug Abuse

PROJECT SUMMARY This application is submitted in response to RFA-DA-26-001: SCORCH Data Mining and Functional Validation. Human immunodeficiency virus (HIV) infects non-neuronal cells in the brain, particularly microglia, which serve as reservoirs of latent infection. HIV has deleterious effects on both non-neuronal and neuronal cell function in brain regions involved in reward, emotion, and cognition. Many of these same regions, including the nucleus accumbens (NAc), also regulate the motivational properties of opioids and other drugs of abuse. Opioid use disorder (OUD) is more prevalent in people living with HIV than in the general population, and HIV and OUD reciprocally interact, with each exacerbating the severity of the other. EcoHIV is a modified HIV strain capable of infecting microglia, macrophages, and CD4+ T cells in mice, and recapitulating key pathobiological features of chronic HIV infection in humans. As part of the SCORCH consortium, we have generated single-nucleus RNA sequencing (snRNA-seq), two-dimensional (2D) single-cell spatial transcriptomic (Spatial-seq), and 3D single- cell Spatial-seq data from the NAc of control and EcoHIV-infected mice that remained drug-naïve or had a history of intravenous (IV) opioid (oxycodone) self-administration. Sequencing data were also collected from the same groups of mice that received antiretroviral therapy (ART). Here, we will mine this unique dataset to investigate the cellular and molecular mechanisms of HIV and opioid interactions in the NAc. In AIM 1, we will analyze our sequencing data to define the genetic phenotypes and spatial organizations of the medium spiny neurons (MSNs) in the NAc that undergo the most robust transcriptional remodeling in response to HIV infection alone and in combination with opioid self-administration. This analysis will enable us to distinguish between D1- and D2-expressing MSNs, identify novel subtypes, and determine their distributions within the NAc according to established (e.g., core versus shell) or novel spatial architectures. We will also integrate our mouse sequencing data with similar datasets collected from HIV-infected and drug-experienced rats, non-human primates (NHPs), and humans, available through the SCORCH-Neuroscience Multi-omics (SCORCH-NeMO) Archive. By constructing a cross-species cell atlas of the NAc, we can prioritize HIV and opioid-responsive MSN subtypes for further analyses. In AIM 2, we will employ cutting-edge circuit mapping, electrophysiological, and molecular approaches to characterize functional adaptations in the genetically defined and spatially organized MSN subtypes that exhibit the most robust transcriptional responses to HIV infection and opioid exposure. In AIM 3, we will use the CRISPR-Cas9 system to target high-priority genes dysregulated by HIV and opioids in genetically defined and spatially organized MSN subtypes in the NAc. The effects of CRISPR-mediated gene cleavage in MSNs on IV opioid self-administration and other NAc-mediated behaviors relevant to HIV/opioid interactions will be evaluated in EcoHIV-infected mice. This highly innovative research program promises to fundamentally advance our understanding of the pathobiological interactions between HIV and opioids.

Minnesota Arts Board

The Minnesota Arts Board awards grants to artists, arts organizations, schools, and communities throughout Minnesota to support artistic creation, arts education, cultural access, and the integration of arts in community life.

Minnesota State Arts Board

Minnesota State Arts Board provides grants to support arts and cultural programming, artist fellowships, arts education, and community-based arts projects across MN.

Missouri Arts Council

Missouri Arts Council provides grants to support arts and cultural programming, artist fellowships, arts education, and community-based arts projects across MO.

NIAID - National Institute of Allergy and Infectious Diseases

SUMMARY Nearly 40 million people globally and 1.2 million people in the United States are living with HIV. Although antiretroviral therapy (ART) has transformed HIV from a fatal disease to a manageable chronic condition, lifelong treatment poses substantial challenges, and ART does not cure the infection. Based on data in humans and non- human primate models linking high quality CD8+ T cell responses with low viral loads, there is strong rationale for targeting HIV-specific CD8+ T cells to promote control of HIV. However, due in part to limitations of existing CD8+ T cell assays, the field currently lacks a mechanistic understanding of which features of the CD8+ T cell response might drive effective control of HIV rebound. The overarching goal of this project is to comprehensively define the mechanistic features of CD8+ T cell responses that most strongly relate to control of HIV after stopping ART. To do this, we will study peripheral blood samples collected before analytic treatment interruption (ATI) and longitudinally after rebound in participants from ATI sub-studies within the San Franscisco SCOPE cohort, including several who maintained low viral loads (<2,000 copies/mL) for several months after stopping ART. We recently developed a novel nanoparticle class I peptide:Human Leukocyte Antigen (pHLA) pool assay that enables simultaneous measurement of pHLA specificity, T cell receptor (TCR) avidity and breadth of peptide recognition, and transcriptional signature at a clonotype level from up to 1000 HIV-specific CD8+ T cell responses per sample. In Aim 1, we will use this tool to identify features of HIV-specific CD8+ T cell clonotypes that respond as HIV reactivates during viral rebound. In Aim 2, we will apply newly-developed single-copy sequencing methods to plasma HIV sequences in order to characterize the development of HIV escape to autologous CD8+ T cell responses during and after rebound. Finally, to connect these distinct but inter-related data types, in Aim 3, we will utilize mathematical models that describe viral dynamics and evolution simultaneously to model dynamic CD8+ T cell-virus interactions that promote control of HIV after ART is stopped. This highly collaborative project with clinical, immunology, virology, and mathematical investigators will identify the mechanistic properties of CD8+ T cell responses required for successful control rebound HIV across a large group of post-treatment controllers. Our work will provide a target for the next generation of immunotherapies for HIV cure and inform T cell-based therapeutics for other chronic infections and cancers.

NIDA - National Institute on Drug Abuse

Project Summary/Abstract Substance use disorders (SUD) pose a major public health crisis that exacts heavy tolls on communities and healthcare systems, yet current survey data remain underutilized due to limitations in conventional analytic methods. This project proposes to develop a novel behavioral foundation model that transforms qualitative epidemiological survey responses into robust, quantitative latent representations of substance use behaviors. By harmonizing data from NESARC-III, NSDUH, and UK Biobank, we will “textualize” both structured and free- text responses into unified narratives that capture the nuanced details of individual experiences. Our approach leverages advanced natural language processing to convert diverse survey data into coherent, machine- interpretable inputs, and fine-tunes state-of-the-art, open-source large language models (LLMs) with integrated demographic tokens to enhance subgroup-specific predictions. We will rigorously validate the model’s performance against established machine learning techniques using metrics such as area under the ROC curve, calibration, and cross-dataset generalizability. Downstream applications include precise risk stratification for SUD outcomes, latent clustering to identify distinct risk and resilience profiles, and data-driven survey instrument optimization. Open-access dissemination of our tools will empower precision public health initiatives, enhance early identification of high-risk groups, and support targeted interventions to reduce the societal burden of substance use disorders.

NIGMS - National Institute of General Medical Sciences

1 PROJECT SUMMARY 2 Successful development of new active pharmaceutical ingredients (APIs) requires synthesizing many 3 structurally related compounds to optimize pharmacokinetic properties related to absorption, distribution, 4 metabolism, excretion, and toxicology. However, the expense of time and resources needed to synthesize each 5 candidate makes API optimization a bottleneck. As a result, researchers have developed a relatively short list of 6 expedient synthetic methods on which they rely to develop APIs. These methods tend to involve fragment 7 couplings that forge new C-C, C-N, or C-O bonds by joining two building blocks, which allows those seeking new 8 APIs to purchase libraries of suitable building blocks and explore their pairwise couplings in modular fashion. 9 The modularity of this approach means that each new fragment increases the quantity of structures that can be 10 explored in a nonlinear fashion. However, some of the most frequent substructures in APIs—saturated medium- 11 sized nitrogen-containing heterocycles—are not well represented in commercial catalogues of building blocks, 12 due to limitations in state-of-the-art synthetic methods used to produce them. The ability to create custom building 13 blocks in a modular fashion, which would enable both more thorough and more efficient structure optimizations 14 of APIs, would represent a significant advance in modern synthetic chemistry. However, current synthetic 15 limitations make exploration of 3D structural variants of these heterocycles difficult. 16 This proposal outlines a strategy to develop new catalytic methods that will convert readily accessible starting 17 materials into structurally complex heterocyclic building blocks in modular fashion. The modularity of the 18 proposed methods, the accessibility of starting materials, and the proposed catalyst control of stereochemistry 19 in these chiral products will make exploration of new, chiral variants of these important building blocks more 20 practical. The proposed research includes a tandem fragment coupling-cyclization approach to assemble 21 multiple building blocks to construct structurally complex, medium-sized, saturated heterocycles. Mechanistic 22 experiments and computational exploration of key mechanistic steps is proposed so that both activity and 23 selectivity of the catalysts can be understood and iteratively improved with the assistance of new data 24 representations and machine learning. Accomplishing these goals would provide practitioners access to diverse 25 structural variants of important building blocks for API development, as well as demonstrate the future role of 26 machine learning as a tool that can accelerate the development of methods with a large scope.

NIAID - National Institute of Allergy and Infectious Diseases

Export of RNA from the nucleus is essential for all eukaryotic cells and has emerged as a major step in the control of gene expression. mRNA molecules are required to complete a complex series of processing events most of which are highly conserved across eukaryotes, reflecting their ancient origin, The mRNA export factor Mex67/NXF1 (yeast/vertebrates) transports its RNA cargo from the nucleus through the nuclear pore complex (NPC) to the cytoplasm on a distinct ATP dependent pathway. In most eukaryotes, Mex67/NXF1 exists as a single protein; however, additional tissue-specific isoforms of NXF1 exist in multicellular organisms (i.e. humans). However, significant deviation from the canonical pathway as described from animals and fungi has emerged in the trypanosomatids, a group of divergent unicellular parasitic protozoa. We recently discovered that Trypanosomes have three very distinct paralogs of Mex67 which we termed TbMex67, TbMex67b and TbMex67L (for Like), with differing roles in mRNA export and ribosome biogenesis. Our focus is on TbMex67 and TbMex67b, which function as general mRNA export factors, albeit also associate with paralog-specific subsets mRNA cargo and differing protein interactomes in the mammalian bloodstream form (BSF) versus the insect procyclic form (PCF) of the organism, reminiscent of the tissue-specific NXF1 variants observed in metazoa. Trypanosomatids lack individual gene promoter control, instead relying heavily on post- transcriptional gene regulation and potentially, making RNA export a crucial component in the control of gene expression. It is our hypothesis that TbMex67 and TbMex67b function to help differentially regulate the expression of genes in different life cycle stages, possibly on alternate mRNA export pathways. To determine this, we will continue to characterize the paralog-specific protein interactomes and RNA cargos of the two Mex67 proteins quantitatively and comprehensively in cells in the different life stages by utilizing and adapting methods we have pioneered, as well as standard biochemical techniques. Our preliminary work has identified putative analogs of the transcription-export complex THO/TREX which has long been considered as absent in these parasites. In addition, we have previously shown that trypanosomes depend on the Ran GTPase system, a major departure from the canonical textbook model of an ATP-dependent mRNA export machinery. We hypothesize that this system will provide a new perspective on how Ran can be utilized to mediate directional transport across the NPC. Our strategy will include classical biochemical techniques involving exogenously expressed components that have been successfully employed to delimit nucleocytoplasmic transport in yeast and humans, as well as state of the art proteomic and structural methods to compute topological maps of the TbMex67-Ran machinery. With significant implications for the mechanisms that control gene expression and hence differentiation, responses to altered environments and fitness as a parasite, these deviations may reveal additional, unsuspected, mRNA export pathways.

NICHD - Eunice Kennedy Shriver National Institute of Child Health and Human Development

Project Summary/Abstract Increasing the number of infants in the neonatal intensive care unit (NICU) who can be fed using mothers’ own milk (MOM) is crucial for reducing expensive co-morbidities experienced by premature and ill infants. Mothers on NICU infants have delayed secretory activation (SA) and challenges to maintain SA, and coming to volume (≥500 mL/d by d 14 postpartum, CTV). However, the biological mechanisms that are involved in inhibiting the initiation and establishment of lactation in this at-risk population are generally poorly understood. SA involves the closing of tight junctions in the mammary gland and the transition to copious milk production. Following this transition, the mammary gland transitions from endocrine to paracrine/autocrine regulation of lactation, leading to an increase in milk volume. Both SA and CTV are critical for initiation and maintenance of lactation, and prior data suggest that both may be impacted by maternal health factors. In our prior work, we found that both transcriptomic gene expression and lipid metabolism are associated with milk production in mothers of term infants later in lactation. However, similar work has not been done during early lactation or in the NICU population. In this project, we will use samples from a highly-controlled parent trial to investigate the molecular and metabolic pathways that are associated with the achievement of SA and CTV in the first 2 weeks postpartum (pp). We will use transcriptomics, as well as biochemical analysis of inflammatory and lipid metabolism pathways to elucidate the biological mechanisms associated with 1) the achievement of SA by week 1 pp and 2) pumped milk volume at 2 weeks in a population of mothers with infants in the NICU. As participants in the parent clinical trial, all mothers will receive consistent, state-of-the art lactation support and care, reducing the possibility of variability in access and quality of care. The results of this study will provide evidence to support the development of future interventions that are targeted to promote sufficient milk production and prevent lactation problems in vulnerable populations.

NIGMS - National Institute of General Medical Sciences

Project Summary Chromatin structure and function are dynamically regulated by ATP-dependent chromatin remodelers and Sirtuin histone deacetylases, two critical enzyme families that play pivotal roles in DNA transcription, replication, repair, and genome stability. Chromatin remodelers use ATP hydrolysis to reposition and modify nucleosomes, while Sirtuins, NAD⁺-dependent histone deacetylases, modulate chromatin states through site-specific histone deacetylation. These enzymes often work in concert to fine-tune chromatin accessibility and gene expression. Although their roles have been studied to some extent, their precise mechanisms and the nature of their interplay remain poorly defined, underscoring the need for further investigation into their complex interactions with chromatin. Building on my laboratory’s strong track record in chromatin biology, structural studies, and functional assays, as well as compelling preliminary data, my research program aims to uncover the individual molecular mechanisms of chromatin remodelers and Sirtuins, as well as focus on their coordination in regulating nucleosome dynamics and chromatin structure. Supported by a highly collaborative network and innovative methodologies, this work aims to tackle fundamental unanswered questions in chromatin biology, with the potential to drive significant advancements in the field Two major themes drive this research. The first explores ATP-dependent chromatin remodelers, specifically CHD and ISWI ATPases, examining their catalytic mechanisms, substrate specificity, and the influence that histone post-translational modifications (PTMs) have on their remodeling activity. State-of-the-art approaches, including high-resolution cryo-electron microscopy (cryo-EM), molecular dynamics simulations, and advanced biochemical assays, will reveal the dynamics of remodeling cycles and interactions with chromatin. The second theme focuses on the Sirtuin family of deacetylases and their interplay with chromatin remodelers. Structural and functional studies, coupled with tools like synthetic nucleosomes with defined PTMs, real-time FRET-based translocation assays, and cross-linking mass spectrometry, will provide unprecedented insights into their coordination and regulatory roles. By leveraging our expertise, robust preliminary data, and a world-class support network, this research will not only advance our understanding of chromatin modulation but will also drive the entire field forward, offering critical insights into gene regulation, genome integrity, and the development of therapeutic strategies targeting chromatin dysfunction in diseases such as cancer and neurodegeneration.

NIAID - National Institute of Allergy and Infectious Diseases

ABSTRACT There are ~40 million people world-wide infected by the Human Immunodeficiency Virus (HIV). In the absence of a functional cure, antiretroviral therapy (ART) represents the primary treatment option against HIV. ART regimens containing the integrase strand transfer inhibitors (INSTIs) form first-line treatments for people living with HIV/AIDS (PLWH). INSTIs work by blocking the function of the viral intasome, which is the nucleoprotein complex that forms on the linear ends of the viral long-terminal repeats and mediates the insertion of viral DNA into host target DNA. Despite significant advances afforded by the inclusion of INSTIs to ART regimens, resistance to even the latest drugs is becoming a greater clinical problem. In the clinical literature, there are specific sets of drug-resistant mutations (DRMs) within the IN protein that arise most frequently to INSTI therapy, including individual mutations E138K, G140A/S, and Q148H/K/R. Eventually, the virus evolves more complex combinations of mutations, including the clinically relevant triple mutants E138K/G140A/Q148K (KAK) and E138K/G140S/Q148H (KSH). In preliminary data, models of HIV fitness landscapes built from viral sequences derived from PLWH suggest that the pathways through which combinations of complex triple mutant KAK and KSH combinations emerge can vary dramatically. However, the underlying basis for how and why distinct DRM combinations preferentially emerge remains unclear. This work will test the fundamental hypothesis that the pathways toward drug resistance evolution can be rationalized using atomic resolution structures, supported by multiple experimental measures of viral fitness. In three specific aims, this work will (i) derive drug- specific pathway orderings for KAK and KSH combinations using tools that measure prevalence-based fitness based on extensive viral sequencing data available from PLWH, (ii) determine atomic structures of HIV intasomes along KAK and KSH pathways using the latest technological advances in cryogenic electron microscopy, and (iii) gain dynamic and mechanistic insights into select DRMs along KAK and KSH pathways. Collectively, the structural snapshots will be ordered along the predicted pathway trajectories and, together with existing fitness measurements and complementary molecular dynamics-based analyses, will begin to rationalize the pathways of drug resistance evolution, as well as the associated mechanisms of drug resistance to INSTI therapy. Although the mechanistic analyses of drug resistance have been interrogated in the past, considerably less attention has been given to understanding pathways of drug resistance evolution. Dissecting both pathways and mechanisms of patient-derived clinically relevant complex DRM combinations that arise in response to treatment will build a foundation for prospectively forecasting the evolutionary trajectories leading to drug resistance. The principles can be extended to other infectious diseases, beyond HIV.

Montana Arts Council

Project grants from the Montana Arts Council support specific arts and cultural projects including performances, exhibitions, arts education, and community arts initiatives that expand public access to the arts in Montana communities.