University Of California Santa Cruz
universitySanta Cruz, CA
Total disclosed
$88,801,150
Award count
164
Distinct programs
3
First → last award
2001 → 2031
Disclosed awards
Showing 76–100 of 164. Public data only — SR&ED tax credits are confidential and not shown.
NSF Awards · FY 2024 · 2024-09
Animal behavior may impact ecology in ways that have lasting effects on biological diversity. In sailfin molly fish, males either court females and allow them to choose whether to mate, or harass females by making sneak mating attempts. This study will address how this common behavioral feature of populations, the maintenance of alternative mating strategies, affects the communities with which they interact? This work addresses whether the frequency of each male type impacts females’ ability to feed on zooplankton. If sneakers are common, females may forage less because of mating harassment, which may increase zooplankton abundance and decrease the phytoplankton that zooplankton eat. In this case, courters may succeed in clear water because their displays are visible, whereas sneakers may have an advantage in turbid water because females cannot see them as easily. Thus, the hypothesized trophic cascade is predicted to make the water clearer, which may, in turn, favoring courting males. If the frequency of courters increases, females may forage more, reducing zooplankton, increasing phytoplankton, and increasing turbidity, and favoring sneaking males. This behavior-ecology feedback cycle may thereby preserve both male types while driving variation at the community level. The proposed work will foster student engagement by building inclusivity-focused collaboration involving multiple institutions and allowing for opportunities to gain meaningful skills in studying behavioral and community ecology. The impacts and outreach include quantifying the effects of hands-on research on student success and sense of belonging and disseminating information about the importance of “eco-evolutionary dynamics”, a process key to the maintenance of biological variation in natural populations, using work on a charismatic and familiar species. Participants will gain direct research and mentorship skills while interacting with peers and mentors from three institutions. The team will publish and present findings and engage in outreach and activities with local organizations committed to enhancing science literacy among the public. The primary goal of this study is to use an eco-evolutionary framework to investigate the effects of variation in mating harassment on top-down ecological control. The study will use the sailfin molly (Poecilia latipinna), a poeciliid fish which exhibits size-dependent sexual polymorphism: small males sneak copulations whereas large males court females. Females are the primary foragers in this system. The work specifically addresses whether mating harassment can perturb top-down ecological control by reducing female foraging rates. The experimental design employs mesocosms with differing morph frequencies to generate different levels of mating harassment. A higher frequency of sneakers is predicted to reduce top-down control, whereas a higher frequency of courters is predicted to increase top-down control. The subsequent effects on the trophic cascade may result in turbidity changes that generate fluctuating selection pressures alternately favoring courting and sneaking morphs, thereby maintaining the polymorphism. The proposed research will provide novel insights into how sexual conflict shapes aquatic communities. The team will use an inclusion and equity-centered approach to engage a diverse cohort of undergraduate and graduate students in research, with a major goal of promoting student success and retention in STEM. This approach will include multiple metrics to quantify the effects of participation in the research program on student success. 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
PypeIt represents a set of tools that enable a user to take data acquired from an astronomical telescope and turn it into a table of numbers that the user can make scientific measurements with. To make this change requires a set of techniques and algorithms that have been developed over many years by many different individuals. PypeIt collects these techniques into a single set of software that allows end to end data calibration. This proposal aims to make it easier for new people to write and maintain this software by breaking it into more manageable pieces. It also aims to increase engagement with astronomers throughout the community so as to increase the number of astronomers who will work on developing the tools as well as the overall user base. More users and more developers will increase the community and make the project self-sustaining in the long term. PypeIt is a large set of python-based libraries and scripts that reduce two-dimensional spectra into calibrated one- and two-dimensional data sets. The core goals of this proposal are to: build a graphical user interface that aids in both running PypeIt and highlighting issues and errors in the data reduction process, refactor the code base so that the underlying core routines are easily accessible to external developers, and build tools that ease cloud-based use of PypeIt, with the goal of quick and efficient reduction of large data sets. Designed and developed in consultation with the community, these GUIs will broaden the science produced by PypeIt, improve the quality of the scientific products, and speed the time to publication. Second, we will refactor the core algorithms. To date, PypeIt has not been designed nor developed with the intent to integrate its core codes within the larger astronomical, software ecosystem. We would refactor the core algorithms, e.g. sky subtraction and the underlying basis spline code, to (i) accept and return basic Python objects, (ii) have extensive documentation on inputs, outputs and the algorithm procedures; and (iii) include usage examples as further documentation and for testing. These efforts will facilitate the future development and maintenance of PypeIt and, more importantly, enable the community to leverage the code for their own purposes and future instruments. This award by the Office of Advanced Cyberinfrastructure is jointly supported by the Division of Astronomical Sciences in the Mathematics and Physical Sciences Directorate. 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
Brown bears (Ursus arctos) have undergone rapid population declines over the last 150 years in the lower 48 states. This project will use DNA sequencing technologies to investigate the effects of this rapid population decline as well as the effects of previous conservation management actions. The researchers will investigate the utility of these genetic technologies for population monitoring and management. New genetic tools will be developed to rapidly sequence and identify individual brown bears in the lower 48 states using non-invasive samples. Samples from both historical (museum) and contemporary populations will be used to better understand the impact of population decline and conservation management efforts on the health of brown bear populations. The project will yield new insights into how small populations of animals can persist and will include a database with applications for general population monitoring and human-wildlife conflict scenarios. This project will also establish a brown bear genetic database and provide training opportunities in genetic and genomic technologies to conservation managers. Genomics is poised to be a potentially useful and cost-effective tool for population monitoring and management, however, the limitations of population genetic estimates for conservation purposes are not well understood. This project will use an extensive set of historic and modern brown bear (Ursus arctos) samples to characterize genomic diversity over the last 200 years, how it has changed over time and whether management decisions (e.g., translocations) have impacted the genomic landscape of the species. Brown bears in the lower 48 have been extensively monitored since approximately 1975. The life history data collected by conservation partners over the past several decades, paired with newly collected genomic data, will be used to analyze the impact of past translocations and population bottlenecks in the lower 48. Relating population genetic statistics to life history traits, such as fecundity, lifespan, and independent population size estimates, will help to better implement recommendations to maintain genetic health for species of conservation concern. This project is jointly funded by the Division of Environmental Biology and Integrative Organismal Systems through the Partnership to Advance Conservation Science and Practice 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 · 2024-09
When machine learning (ML) and artificial intelligence (AI) techniques are used in applications involving humans (e.g., recommending personalized items to users, ranking candidates for admission, hiring, and lending), it is critical to ensure safety for both the learning system and humans. From the learner’s perspective, the ML system should prevent manipulated information from disrupting the training procedure (safe training) and remain robust against rare and unexpected events during deployment (safe deployment). From the human standpoint, it is crucial that ML decisions align with social values (safety perception) and prevent the system from evolving toward unsafe states (safe downstream effects). However, achieving such safety assurance is often challenging due to the complex interactions and feedback dynamics between humans and the learning system. For instance, humans who utilize for obtaining loans or job searches may change their behavior, such as changing their profiles, to achieve favorable outcomes. While digital platforms offering on-demand services may steer consumer preferences to benefit their service. Meanwhile, as the users evolves, the learning system needs to update accordingly. Under such intricate human-AI interactions, creating a safe learning environment that supports long-term human well-being remains a significant challenge. This project aims to develop theoretical and algorithmic foundations for building a human-AI ecosystem with long-term safety assurance. The outcomes have the potential to benefit diverse domains, including lending, recruitment, healthcare, admission, and recommendation systems. To achieve long-term safety in the human-AI ecosystem, the project explicitly considers the complex interactions between humans and the learning system, with a research agenda comprising the following objectives: 1) Develop an analytical framework to characterize human-AI interactions, which embeds all safety components for both the learner and human agents; 2) Examine the feedback effects between agents and the ML system, developing methods to ensure the long-term safety of both under their dynamic interactions; 3) Establish a causal understanding of human-AI dynamics and design transparent and interpretable interventions to achieve long-term safety. This agenda entails developing new theories and algorithms at the intersection of control theory, reinforcement learning, dynamical systems, and optimization. Beyond theoretical and algorithmic contributions, the project will be validated through various use cases, including recommendation systems, lending, and healthcare. 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
Stellar astrophysics, pivotal for understanding stars from their inception to demise, holds significant implications for life on Earth and beyond. Our Sun, vital for terrestrial ecosystems, also poses risks through solar flares that can disrupt modern technology. This project aims to enhance stellar models by simulating turbulent plasma flows within stars using cutting-edge computational tools. By refining our understanding of these dynamics, this project aims to improve predictions of stellar evolution and to better comprehend and mitigate solar impacts on Earth. This investigation supports a commitment to diversity and education in STEM fields. The Principal Investigator's involvement in NSF S-STEM programs will provide undergraduate and master's students with hands-on research experience, fostering the next generation of scientific leaders. Through leadership roles in prestigious summer programs, the PI aims to empower women in geophysical fluid dynamics and theoretical astrophysics, ensuring a diverse and inclusive future for these fields. This research team aims to advance stellar astrophysics by refining the rotational mixing models crucial for stellar evolution codes. They will address its limitations through direct numerical simulations and multiscale asymptotic analyses. Specifically, they will map the parameter space governing rotational turbulence, integrating complex factors such as stellar rotation profiles and buoyancy frequencies. The project further aims to incorporate the influence of convective zones on differential rotation, a factor currently overlooked in existing models. These innovations will culminate in a new generation of rotational mixing models, implemented and validated within the MESA framework. By rigorously testing against asteroseismic observations, this project aims to provide the astronomical community with more accurate tools to decipher stellar interiors and evolutionary pathways. 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
Computer networks, from wireless to the Internet, are crucial enablers of the United States economy and industry, and of many applications important to society, such as education, healthcare, and workforce development. As such, scientific research on this topic explores new innovations that have the potential to improve the performance and cost of such networks. This project is focused on network functions (NFs), which are crucial for managing networks and enhancing user experience from different perspectives such as providing low-latency applications and stronger security guarantees. Supporting multiple NFs simultaneously on a single network device or multiple heterogeneous devices, while minimizing resource usage and maximizing throughput, has gained significant attention. However, manually managing these co-existing NFs is labor-intensive and unsustainable. This project aims to design efficient tools that automatically manage the algorithm design, deployment and resource management of multiple co-existing NFs through a new concept called consolidated data planes. These management tools will allow network operators to efficiently handle co-existing NFs, optimizing resource usage and throughput, and thus reducing economic costs. This project proposes consolidated data planes based on the finding that there is a huge space for optimization if efficient and space-compact data structures and algorithms considering multiple NFs can be designed. It achieves its goals through the following: 1) An automatic tool to construct consolidated data plane programs for multiple NFs; 2) Deployment of consolidated data plane programs to meet the NF objectives and the resource limitations of the network devices; 3) Network-wide management of consolidated data plane resources. The proposed design will be fully implemented and evaluated on a Tofino switch platform at the University of Connecticut and the University of California Santa Cruz, as well as a heterogeneous devices platform on CloudLab. This project will introduce a new research direction about programmable data plane algorithms that potentially impact network algorithm research. This project will also result in the development of open-source tools to manage co-existing NFs effectively. 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
Non-Technical Summary To advance the national health, prosperity, and welfare, and to promote the progress of science in the United States, the objectives of the proposed REU site, which is funded by the Division of Materials Research at the NSF, are to increase the retention and graduation rates of students in the STEM disciplines, and furthermore, to encourage students to pursue post-graduate degrees in science and engineering. These objectives are achieved by focusing on recruiting students attending two- and four-year primarily undergraduate institutions and non-Ph.D. granting institutions, and then identifying talented prospective participants, based on their academic record, letters of recommendation, and short essays, who should be encouraged to attend graduate school at a later stage. The program participants engage in interdisciplinary research of materials that could be used in low-power electronics, the health sciences, and other technological fields where sustainability (especially energy efficiency) is important. The research projects will be carried out under the auspices of the Materials Science and Engineering Initiative at the University of California, Santa Cruz, culminating with participation in a Research Symposium at the end of the program. Professional development activities include safety training, responsible conduct of research, impostor syndrome, graduate school application planning workshops, and sexual harassment/harassment workshops and training. The program will be augmented by a partnership with the UCSC Cal-Bridge program. Technical Summary The objectives of the proposed REU site are to increase the retention and graduation rates of US students in the STEM disciplines, and furthermore, to encourage these students to pursue post-graduate degrees in science and engineering. These objectives are achieved by focusing on recruiting students attending two- and four-year primarily undergraduate institutions and non-Ph.D. granting institutions, and then identifying talented prospective participants, based on their academic record, letters of recommendation, and short essays, who should be encouraged to attend graduate school at a later stage. The program participants engage in interdisciplinary research of materials that could be used in low-power electronics, the health sciences, and other technological fields where sustainability (especially energy efficiency) is important. The research will focus on methodologies to study the fundamental properties of materials that in the future may be used in energy-efficient electronic and optoelectronic devices, bioelectronic devices, and new ways of storing and using renewable energy. The research projects will be carried out under the auspices of the Materials Science and Engineering Initiative at the University of California, Santa Cruz, culminating with participation in a Research Symposium at the end of the program. Professional development activities include safety training, responsible conduct of research, impostor syndrome, graduate school application planning workshops, and sexual harassment/harassment workshops and training. The program will be augmented by a partnership with the UCSC Cal-Bridge 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.
NIH Research Projects · FY 2025 · 2024-08
PROJECT SUMMARY Successful motor skill learning is marked by decreased performance variability over time. For motor skills learned during early developmental time periods, such as walking and talking, performance remains highly stable and precise throughout life, suggesting that associated motor circuits exist in a stable state that is tuned to performance. Motor skill stabilization has been studied in terms of changes to neural population coding, neurophysiology, and synaptic plasticity, yet the molecular mechanisms that transition motor circuits to a state that supports stable motor performance are unknown. Like developmental motor skills in humans, the song of the Bengalese finch, an established animal model for the neural mechanisms supporting skill learning, is learned over the first few months of life, becomes less variable and plastic over time, and remains highly stable throughout a bird’s life. Birdsong is controlled by a dedicated neural circuit whose connectivity, neuronal composition, and molecular properties are similar to those of cortical motor circuits in mammals. The objective of this project is to leverage the experimental accessibility of the birdsong neural circuit and the highly quantifiable nature of birdsong to define the molecular mechanisms that regulate the transition from variable to stable motor skill performance. Recent advances in genomics and single-cell molecular assays have enabled genome-wide, cell-resolved analyses of how the molecular attributes of the birdsong neural circuit change during song learning and performance. Our preliminary data indicate that birdsong stabilization is associated with a suite of transcriptional changes in the birdsong neural circuit. In the proposed research, we will test the hypothesis that song stabilization is associated with closure of neuronal epigenetic state in song motor regions using single-nucleus gene expression and chromatin accessibility assays combined with histone modification profiling (Aim 1). We will then characterize the roles of two candidate molecular systems, one governed by a transcription factor and the other a neuropeptide pathway, in regulating the maturation of song circuitry and the stabilization of song (Aims 2 and 3). First, we will characterize the role of the homeodomain transcription factor SIX2, whose expression is dynamically regulated during song stabilization, in establishing projection neuron identity in a cortical song motor region using gene expression manipulations, transcriptomics assays, and sensitive analyses of birdsong variability (Aim 2). Finally, we will determine the role of the corticotropin releasing hormone (CRH) neuropeptide system in regulating the developmental balance between song stability and variability (Aim 3). Together, the proposed research will shed light on the molecular mechanisms that regulate motor stabilization and reveal candidate factors whose dysfunction underlie developmental motor disorders.
NSF Awards · FY 2024 · 2024-08
The overarching objective of this award is to improve our understanding of extragalactic gamma-ray photons from blazars and the detection of these photons by Imaging Atmospheric Cherenkov Telescopes (IACTs). The project will study the highest energy electromagnetic radiation from blazars in multiple ways. Gamma-ray emitting blazars are among the most extreme astrophysical sources within the Universe, harboring energetic phenomena far beyond that attainable by terrestrial accelerators. These objects are prime laboratories for multi-messenger astrophysics, as they are hypothesized as progenitors of every messenger so far measured, including photons, neutrinos, ultra-high-energy cosmic rays and gravitational waves. This multi-component project uses data from the VERITAS and prototype Schwarzschild-Couder (pSCT) telescopes to increase our understanding of gamma-ray photons from blazars by probing fundamental and observational questions about the entire gamma-ray photon path, from the creation of the photon and its interactions along its extragalactic travels, to the detection of the gamma-ray by current and future IACTs. Specific investigations focus on production of gamma rays within the blazar itself, quantification (by proxy) of the photon interactions along the extragalactic path, and improvement of gamma-ray detection by current and future IACTs. The project will help to educate and train the next generation of US gamma-ray astrophysicists, supporting a graduate student and undergraduates as they take part in cutting edge research. The team will explore ways to improve the diversity, equity and inclusion practices within large scientific collaborations such as VERITAS and the future Cerenkov Telescope Array. This project advances the objectives of "Windows on the Universe: the Era of Multi-Messenger Astrophysics", one of the 10 Big Ideas for Future NSF Investments. 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
Scientists use measurements of shaking produced by earthquakes to understand the physics of underlying earthquake sources and to mitigate related hazards. Observations suggest that the total amount and properties of the energy carried by seismic waves may systematically differ for earthquakes produced in different fault settings, such as for large earthquakes occurring on subduction zone faults, like in Japan and Alaska, or major continental faults, like the San Andreas Fault in California. Dr. Lambert and his students will use physics-based computational models of earthquakes in an effort to explain these differences. They will investigate how different physical properties of faults and earthquake ruptures affect the resulting seismic waves, and conversely, how recordings of earthquake ground motions may be used to infer properties of the earthquake fault zone and the rupture. The research findings will help scientists estimate shaking from future great earthquakes, which is vitally important for earthquake hazard assessment and improvement of seismic building codes. This project provides support and training for an early-career scientist and several undergraduate and graduate students. The energy radiated from earthquake sources as seismic waves is a crucial parameter in earthquake physics and a direct input for the resulting strong ground shaking highly relevant to seismic hazard assessment. Observations suggest that, for a given size of the earthquake source, the total amount of radiated energy may systematically differ for earthquakes in different tectonic settings, such as subduction megathrusts and continental transform faults. The frequency content of seismic radiation is also inferred to systematically vary with source depth, with stronger higher frequencies originating from greater depths. Such differences in the amount and attributes of radiated energy between different fault regions raise questions about potential systematic differences in fault conditions and driving physics of large earthquakes, as well as scaling relationships used to estimate shaking, particularly if such scalings differ between tectonic settings. This project aims to improve our understanding of large earthquake scenarios in different tectonic plate boundary settings by developing physics-based computational models that reproduce a range of geophysical observations. The team will use these simulations to (1) examine what attributes of the resulting earthquake seismic radiation may discriminate between physical models of major faults; (2) characterize fundamental ingredients that affect seismic radiation, particularly those that generate high-frequency ground motions; and (3) develop plausible earthquake scenarios and corresponding seismic radiation inputs for strong ground motions. The simulated earthquake sources will serve as research tools representing 'ground truth' to explore discrepancies between the actual source properties determined directly from the simulations, and estimates derived from applying traditional observational techniques. This will allow a better understanding of how seismic signatures relate to the properties and behavior along natural faults and how to design optimal observational arrays to resolve important aspects of the earthquake source process. 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 is a project jointly funded by the National Science Foundation’s Directorate of Geosciences (NSF-GEO) and the Israel Binational Science Foundation (BSF) in accord with the language in the Memorandum of Understanding between the NSF and the BSF. This Agreement allows a single collaborative proposal, involving US and Israeli investigators, to be submitted and peer-reviewed by NSF. Upon successful results of the NSF merit review and recommendation by the cognizant NSF Program of an award, each Agency funds the proportion of the budget and the investigators associated with its own country. The study of seismic waves is the most commonly used tool to investigate the mechanics of earthquakes. Earthquakes are described by parameters such as the seismic stress drop, seismic moment and radiated energy that are typically derived through the analysis of seismograms at great distances from the earthquake. These measurements play a crucial role in understanding the earthquake rupture process, risk and hazard assessments. However, they all rely on fundamental assumptions associated with the earthquake process and seismic wave travel which are necessary in the absence of any more direct information about the mechanical processes involved in earthquake rupture. Our understanding of earthquake rupture dynamics is based largely on seismic measurements and corresponding estimations of these parameters. Here we propose a series of experiments to directly measure fault rupture dynamics on the interface at the same time as taking seismic data in the laboratory. This project uses one of the only apparati in the world capable of the high-speed imaging required and combine that data with in-situ seismograms to develop a unique capability that can test and extend the uses of seismology for studying earthquakes. This project will foster an international collaboration with Hebrew University, building ties and intellectual exchange between scientists studying earthquakes on two of the highest risk and analogous systems on Earth: The Dead Sea Fault and the San Andreas Fault. This project focuses on a quantitative analysis of Acoustic Emission (AE) signals, which is a laboratory-scale counterpart to seismic measurements, coupled with direct and real-time dynamic rupture measurements derived from high-speed imaging in one of the only laboratories in the world capable of such measurements. This data will be used to address three major targets of observational seismology: magnitude predictability, rupture velocity and its covariance with earthquake size, and radiated energy. Providing a stronger foundation for interpreting these fundamental features of seismograms will allow more information to be gained from the seismological wavefield. The projec tinvestigates three targets and associated ongoing questions related to earthquake source parameters estimations: (1) Magnitude predictability: How early in the nucleation phase of an ideal fault surface can we estimate the size of a rupture? How is the likelihood of having a large magnitude earthquake affected by the presence of barriers? (2) Rupture velocity and its covariance with rupture size: Can observed seismograms be related to the rupture velocity profile? How does the variation in rupture velocities correlate with the final size of the rupture? (3) Radiated energy: Can the common range of scaled radiated energy for observed earthquakes be reproduced in the lab by using specific distributions or densities of barriers? Thus, can the ability to interpret natural observations of radiated energy be increased to infer fault asperity distributions, which in turn have implications for magnitude distributions? 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
Pulsars are rapidly spinning, highly magnetized neutron stars formed from the explosions of massive stars, emitting radiation across the electromagnetic spectrum. Despite extensive studies over six decades, their mechanisms remain incompletely understood. Recent gamma-ray observations have challenged existing theories of high-energy pulsar emission, and the joint detection of gamma rays and gravitational waves from merging neutron stars highlighted the potential of multi-messenger observations of such exotic objects. This award supports researchers at the University of California, Santa Cruz, to conduct multi-messenger studies of pulsars, focusing on their highest energy emissions, gamma-ray variability, and gravitational wave emission. This requires analysis of data from the High-Altitude Water Cherenkov (HAWC) Observatory in Mexico, an international collaboration of thirty institutions, along with data from both space- and ground-based experiments. The work involves graduate, undergraduate, and possibly high school students, working in a stimulating environment which will encourage their participation in one of Mexico's premier scientific experiments. With their extreme properties (e.g. density, magnetic field strength), and stable timing signatures, pulsars have intrigued scientists since their discovery in the late 1960s. GeV and TeV observations challenge existing theories, and along with joint detection of gravitational waves from merging neutron stars, suggested using these exotic objects as probes of fundamental physics, such as possible Lorentz invariance violations. HAWC has a large field of view and a high duty cycle and has been operational since 2015. Its broad survey of the Northern Hemisphere TeV gamma-ray sky has detected dozens of sources, many of which are coincident with known Fermi-LAT gamma-ray pulsars. This project involves a comprehensive joint analysis of Fermi-LAT, HAWC, and LIGO/Virgo data to study the highest energy pulsar emission, and search for possible gamma-ray variability and gravitational wave emission coincident with pulsar glitches. This project advances the goals of the NSF Windows on the Universe Big Idea. 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.
- How ribosomal silencing promotes chronic infection of the gastric pathogen Helicobacter pylori$42,795
NIH Research Projects · FY 2025 · 2024-07
Project Summary: Helicobacter pylori is a bacterial pathogen that infects nearly 50% of the global population and establishes disease-causing infections in the gastric epithelium. H. pylori infections are cured using so- called triple antibiotic therapies, but these fail to eradicate H. pylori in approximately 20-25% of treated patients. Chronic H. pylori infections cause severe gastrointestinal illnesses, gastric adenocarcinomas, and gastric mucosal lymphomas. Despite the devastating consequences of uneradicated H. pylori infections, the mechanisms that allow H. pylori to persist are not well characterized despite the pathogen’s contribution to the disease. Due to increasing in vivo evidence from clinical trials and gastric mucosal biopsies, the field presently proposes that low-growth states such as biofilms facilitate chronic infections in the host. H. pylori biofilm growth is not fully characterized, but our lab showed that genes for ribosomal proteins and ribosome regulators are differentially expressed between biofilm and non-biofilm growth. A gap in knowledge in this field is how H. pylori regulates its ribosome population in low-growth states such as biofilms, and what advantage this regulation confers particularly to maintain chronic infections. My proposed research will address this mechanistic knowledge gap and provide necessary fundamental understanding into how ribosomes are regulated under growth-limiting conditions and in the host. The long-term objective of this study is to determine how H. pylori utilizes ribosomal silencing to regulate ribosome assembly, survive stresses in the host and maintain chronic infections. Preliminary studies show that rsfS, the only known ribosome silencing factor in H. pylori, is required for growth limiting conditions, biofilm growth, and long-term in vivo colonization. The hypothesis for this study is that RsfS is utilized in low growth states to regulate the ribosome population so that H. pylori can maintain chronic infections and survive eradication. The approach will be to expand upon preliminary findings by determining the temporal expression and control elements of rsfS under growth limiting conditions and further investigate the role of rsfS expression in vivo. AIM 1 will identify specific growth limiting conditions in which ribosome silencing is being utilized by defining the conditions that lead to differential rsfS expression and affect the ribosome population. AIM 2 will further define the role of rsfS expression in long-term in vivo infections to help identify the stage of infection that H. pylori utilizes ribosome silencing. The rationale for the proposed aims is that the findings will elucidate mechanisms that allow bacteria in chronic infections to persist so that more effective therapeutic strategies can be developed. The contributions from the fulfillment of these aims will be significant because they will provide fundamental insight regarding H. pylori ribosome populations in low-growth states, test the field’s current model that proposes low growth states are used in chronic infection, and define the role of an essential physiological mechanism required by H. pylori to maintain disease-causing infections.
NSF Awards · FY 2024 · 2024-07
This project aims to serve the national interest by establishing a successful experiential learning program for computer science students from Historically Black Colleges and Universities (HBCUs). The experiential learning activities will be designed with the goal of strengthening and diversifying the open source workforce which is critical to shaping an equitable technological future. From security to infrastructure, open source is at the core of most modern technology. Recent years have seen increased investment from both the private and public sectors in supporting the creation of academic Open Source Program Offices (OSPOs), cultivation of academic open source ecosystems, and cross-sector collaborations with industry and nonprofit. This project specifically engages undergraduate students from underrepresented groups who have completed foundational computing coursework but are still evaluating STEM career prospects. A key outcome is for more HBCU graduates to have the skills, experience, and technical portfolio necessary to transition directly into open source roles; this means a workforce more reflective of the people its technology serves, and given the community-driven nature of open source, one where professionals can directly impact issues they care about. This project aims to achieve the following primary goals; 1) expose HBCU students with foundational computer science skills to open source career opportunities, and 2) equip participants with workforce-preparatory skills not commonly found in undergraduate computing programs, and which especially benefit a career in open source. This project reflects a collaborative effort between a research university Open Source Program Office, an HBCU, and two industry partners in open source. The researchers have completed a pilot program serving four undergraduates from a single HBCU and seek to scale to serve up to 48 students from six HBCUs over three summers. Participants will learn about open source software career pathways by actually contributing to real world open source projects aligned with their interests. Contributor Catalyst combines in-person and remote modalities (mirroring real world employment conditions), situated learning through scaffolded activities, competitive compensation, and multiple layers of cohort support. Learning is further supported by a layered community of practice, including alumni, program, and industry/project mentors. The researchers plan to iteratively refine, assess, and document the program such that other institutions can adapt it to their own contexts in the future. Project results will be disseminated via publication, presentations and online repositories. The NSF ExLENT Program supports inclusive experiential learning opportunities that provide cohorts of diverse learners with the skills needed to succeed in emerging technology fields. 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
Nontechnical abstract: This project addresses the lack of fundamental understanding of chaotic quantum phenomena in two-dimensional (2D) materials, which are a promising platform for the next generation electronics. Chaos is found everywhere in our classical world, causing havoc in various facets of our everyday lives such as long-term weather forecasts and financial market predictions. The quantum analog of chaos remains puzzling and significantly impacts electrons hosted in nanoelectronics based on 2D materials. To this end, the research team uses high precision scanning probes that can image and manipulate electrons at the atomic scale to study and harness chaotic quantum phenomena hosted in 2D materials. This experimental work is strongly supported by advanced and specialized computer-based simulations. In particular, this project focuses on two types of quantum-chaotic phenomena known as quantum scarring and superwire channeling. Quantum scarring originates from the constructive interference of electrons as they traverse nanoelectronic devices and can favor certain unstable pathways in an otherwise chaotic system. Superwire channeling consists of dynamic “wires” that gently guide electrons in patterned channels several nanometers wide, and perhaps microns or even centimeters long. The harnessing of these chaotic phenomena enables novel methods for selective and flexible delivery of electrons at the nanoscale; thus, innovating new modes of quantum control. Additionally, this project involves graduate and undergraduate student research training. Students contribute to project research activities and, in doing so, contribute to senior thesis/doctoral dissertation graduation requirements. These outcomes and their dissemination contribute to the development of a workforce that is proficient with core concepts in quantum mechanics. Technical abstract: This project seeks to enhance fundamental understanding of quantum chaotic behavior in emerging two-dimensional (2D) material heterostructure devices. This is important because chaotic behavior is ubiquitous in nature and so, such phenomena is present in 2D material heterostructure devices. A central activity of this project is the visualization, characterization, and control of quantum scarring and superwire channeling. Both phenomena were first predicted by the theory component of the research team but have yet to be experimentally realized. The research team utilizes scanning tunneling microscopy and quantum dots based on monolayer and bilayer graphene to realize and investigate quantum scarring with unprecedented spatial resolution. Numerical analysis is then employed to illuminate experimental findings and guide the control of these states via the application of electric and magnetic fields and the careful incorporation of atomic scale impurities. For superwire channeling the experimental component of the research team uses a combination of advanced nanofabrication techniques and cutting-edge scanning probe microscopies to probe the predicted zero resistivity of these states. This alluring property can be leveraged for new low power nanoelectronic devices. 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
The Secure and Trustworthy Cyberspace (SaTC) program, a flagship initiative by the National Science Foundation (NSF), addresses critical cybersecurity challenges from a socio-technical perspective. By delving into deep scientific and engineering issues and considering human behaviors, SaTC aims to advance the field of cybersecurity and privacy. The PI meeting will highlight research accomplishment made by the SaTC funded researchers and create a venue to stimulate coordination and collaboration amongst SaTC PIs working on different topic areas and cross disciplines. Breakout sessions, and networking opportunities will foster creativity and help carve out novel research directions. PIs can explore interdisciplinary research opportunities beyond their own study domains. Two-day intense interactions among researchers from different disciplines will lead to new insights, cultivate new collaborations, and help create new research ideas on improving education, recruitment, and career development in cybersecurity. The proposal seeks PI support for developing the program for the two-day bi-annual PI meeting to bring together researchers from across the Secure and Trustworthy Cyberspace (SaTC) program in the fall of 2024. The PI will serve on the organizing committee to develop the 2-day PI meeting program who includes tasks such as identifying speakers, defining breakout topics, as well as selecting highlighted NSF projects. 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 Noroviruses are a top cause of acute gastroenteritis globally, and no approved norovirus vaccine exists. The norovirus capsid protein plays key roles in virus attachment and entry into host cells and is the target of neutralizing antibodies. Recent genomics and serological studies predict the presence of a new antigenic site, named antigenic site G, and suggest that it became immunodominant during the emergence of the most recent GII.4 norovirus variant outbreak, revealing a novel mechanism for virus evolution immune escape. However, the molecular interactions of neutralizing antibodies targeting this immunodominant site on the norovirus capsid have not been described. Our goal is to define the epitopes that are recognized by neutralizing monoclonal antibodies targeting the immunodominant antigenic site G on the norovirus capsid and to directly visualize and map antibody immunodominance in serum antibodies targeting past and current norovirus variants. Using an integrated structural and biophysical approach, we will pursue two specific aims to (1) Define the epitopes of neutralizing monoclonal antibodies targeting the norovirus capsid antigenic site G and (2) Directly visualize the chronological shift in antibody immunodominance towards antigenic site G. Results obtained by this work will provide a molecular roadmap for the development of novel norovirus vaccine immunogens that broadly protect against norovirus infection and disease.
NIH Research Projects · FY 2025 · 2024-07
Project Summary. This award is sought to support the foundation of a research program that will broadly capitalize on the unique properties of inorganic compounds to afford medicinal solutions that are complementary to those accessible via traditional organic medicinal chemistry. The underlying philosophy of the research program is that the historic and continued success of the medicinal chemistry enterprise derives from the diversity of structures and reactivities that can be accessed using organic chemistry. This diversity notwithstanding, there is a greater diversity of properties that can be accessed using inorganic compounds in addition to organic ones. There will be instances in which the chemistry of inorganic substances, or the methodologies and approaches of inorganic chemists, will allow problems to be solved that would otherwise remain intractable. During this award period, the problems that will be tackled are: (i) the lack of an antidote for carbon monoxide poisoning, and (ii) a gap in the understanding of the chemistry and biology of antimony-containing drugs that are widely used to treat the neglected tropical disease leishmaniasis. The need for an antidote for carbon monoxide poisoning stems from the fact that conventional oxygen administration cannot clear carbon monoxide from the body quickly enough in cases of severe poisoning. My research group has previously obtained proof-of-principle data indicating that a small-molecule iron-porphyrin platform can exhibit the chemistry needed by an antidote. I propose to explore this modular platform to uncover the relationships that govern carbon monoxide sequestration and biological efficacy. The parasitic disease leishmaniasis is widely treated with two antimony-containing drugs. Although effective, treatment with these drugs is accompanied by severe side effects. Efforts to improve upon these drugs are hampered by our lack of knowledge concerning their chemistry and biology. We have recently demonstrated that a range of physical inorganic techniques can be used to gain insight into the chemistry of antimony compounds, and we will apply these methods to the antileishmanial drugs. A particular focus will be placed on uncovering the molecular structures of the drugs and their biotransformation products and establishing spectroscopic signatures that will allow these transformations to be followed in complex biological media and environments. Although distinct, these two areas of investigation both center on problems that require a combined expertise in fundamental inorganic chemistry, medicinal bioinorganic chemistry, and biological chemistry. My past training, complemented by key collaborations, will allow me to establish an impactful research program in medicinal inorganic chemistry.
NIH Research Projects · FY 2025 · 2024-07
Project Summary Telomeres are essential structures located at the ends of linear chromosomes that protect genomic integrity by preventing chromosomal fusion, degradation, and activation of DNA damage response pathways. The telomerase reverse transcriptase maintains telomere length to compensate for telomere erosion by adding short DNA repeat sequences to chromosome ends. In the absence of telomerase, telomeres progressively shorten with each cell division due to the end-replication problem and nucleolytic processing. Critically short telomeres ultimately induce cellular senescence or apoptosis. Dysregulation of telomere homeostasis has been implicated in many human diseases, including cancer and rare genetic syndromes. Yet, the molecular mechanisms underlying telomere/telomerase biology and the interplay between telomere dysfunction and disease pathology are still not fully understood. With our previous NIGMS funding, we investigated telomeres/telomerase from ciliates, yeasts, and vertebrates to uncover conserved structural features of telomerase RNA, protein subunits, and telomere DNA. We used a combination of biochemical, structural, computational, and novel single-molecule biophysical methods to study the function and dynamics of telomerase and telomere DNA. Our results, together with the progress made in other laboratories, advanced detailed mechanistic models for telomerase enzyme assembly, spatiotemporal regulation of telomerase recruitment to telomeres, telomere chromatin remodeling by shelterin proteins, and coordinated conformational changes within telomerase during its complex catalytic cycle. We are now uniquely positioned to critically evaluate these models with our established state-of-the-art methodologies. The insights gained from this research will provide a framework for the development of new therapeutic strategies and preventive measures for telomere-related disorders. Funding from the MIRA will provide the necessary resources and flexibility to pursue new avenues of mechanistic research within the rapidly developing field of telomere and telomerase biology.
NSF Awards · FY 2024 · 2024-07
Over a century ago, the Research Vessel Albatross collected fishes from the Philippines, now stored at the Smithsonian Institution. The archive provides the potential for rare insights into how fish have evolved in response to fishing, habitat loss, and other challenges. The research will compare historical and modern fish and will focus on blue sprat, a small coastal species important for food. The research findings can help understand adaptation across many species facing similar challenges. The project will also support paid research internships for students with limited access to careers in science. The project will host workshops to build international exchange with the Philippines. Finally, this research can inform fisheries by identifying fishing zones and where seafood was caught. This project will help to understand the architecture and genomic origins of rapid adaptation, in part by testing the hypothesis that local adaptation provides the raw material for rapid evolution through time. Species objectives include to 1) assemble and annotate high-quality genomes to understand genetic architecture in blue sprat (Spratelloides delicatulus); 2) resequence the genomes of ~1000 individuals across at least five sites in historical and modern eras to identify loci targeted by spatially divergent or temporal selection, and 3) measure morphology and growth to test for the functional importance of genomic variation. The project will focus on historical (1907-1909) samples held by the Smithsonian Institution and modern samples collected in collaboration with Silliman University. The ethanol preservation by the R/V Albatross is a unique scientific accident that provides excellent DNA preservation over the last century. 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
The Santa Cruz Developmental Biology Conference 2024 (SCDB) brings together scientists, researchers, educators, and students to explore unifying principles of development and homeostasis in a broad diversity of animal and plant species. The conference fosters interdisciplinary collaborations that will lead to innovative solutions for accelerating scientific breakthroughs with immediate implications for reproductive and regenerative medicine. The SCDB meeting plays an important role in training the next generation of developmental biologists, by providing a platform for trainees to present their research. These opportunities inspire and equip students with a set of skills to pursue diverse careers in life sciences. Additionally, the conference aims to help equip the next generation of developmental biologists to serve as professional stewards for our society and planet through one of its broader impact activities- the organization of a workshop focused on communicating science and building sustainability into research labs. Enhanced communication to the lay-public and awareness of the environmental impact of scientific research will motivate researchers to incorporate sustainably-minded practices into their work culture. Additional broader impact activities include travel support for 30 participants from historically excluded groups and early career stages. SCDB serves as a catalyst for scientific innovation, education, and societal benefit. Its impact extends beyond the scientific community, contributing to public health and education by fostering a more knowledgeable and scientifically engaged society. Fundamental research in developmental biology has transformed our understanding of congenital diseases, stem cell biology, oncology, and regenerative medicine. Ongoing work at the cutting edge of this field promises to provide novel insights in the years to come, with important implications for our understanding of genetic, molecular and cellular processes of multicellular life, and with important implications for understanding how interacting developmental processes give rise to emergent properties that result in the development of complex phenotypes and structures. The 2024 meeting is focused on unifying principles of organismal development and a group of leading scientists have been invited to discuss diverse experimental and theoretical developmental models across diverse organisms. To address fundamental challenges of development of multicellular life, the 2024 meeting is organized around the following integral topics: Cell-Cell Communication, Theory and Modeling in Development, Active Matter and Mechanics, Convergent and Divergent Morphogenesis, Cellular Transitions and Plasticity, Information Processing and Gene Regulatory Networks and New Technologies and Synthetic Approaches. Broader impact activities include workshops on both scientific communication and designing environmental sustainability into research labs to prepare the next generation of developmental biologists to serve as stewards for society and our planet. This proposal will financially support members of historically excluded groups to be able to attend the meeting. In sum, the 2024 meeting will build on past successes while incorporating best practices for inclusive conferences, highlighting recent breakthroughs, and serving as a catalyst for new approaches and ideas in this rapidly evolving field. 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.
- Localized translational dysregulation in an autism spectrum disorder model using in situ cryo-EM$443,121
NIH Research Projects · FY 2024 · 2024-07
ABSTRACT/PROJECT SUMMARY We propose to leverage innovative in situ cryo-electron microscopy (cryo-EM) techniques to study dysregulated protein synthesis, termed translation, in an autism spectrum disorder (ASD) model. Dysregulated translation disrupts normal neuronal plasticity, leading to various disorders including autism spectrum disorder (ASD), major depressive disorders, chronic pain, and other pathologies affecting millions worldwide. However, a comprehensive understanding of location-dependent ribosome regulation, which plays a crucial role in plasticity, remains elusive. Current methods to study single events at a high resolution in cells are limited, hindering the acquisition of this essential knowledge. We will overcome this limitation using correlative fluorescence microscopy and in situ cryo-EM. The loss of the Fragile-X mental retardation 1 (FMR1) gene product, known as FMRP, is responsible for the most prevalent form of heritable ASD. FMRP interacts with polysomes within two types of RNA granules: fragile X granules (FXGs) and neuronal RNA granules (nRNAgs), also known as "transport granules." Excessive translation resulting from the absence of FMRP has been associated with long-term memory impairment, supported by the notion that neuronal granules contribute to memory and synaptic plasticity. Despite its broad importance in neuronal function, the pleiotropic nature of FMRP has prevented the field from developing a unified understanding of its functions and its underlying role in local translation. To address this, we will develop novel high-resolution approaches to unravel the functions of FMRP in translation within neuronal models. These advances will pave the way for investigating FMRP's involvement in translational regulation using disease models derived from human induced pluripotent stem cells (iPSCs). We propose in this project to apply cutting-edge cryo-EM methods and develop effective workflows in two Specific Aims: In Aim 1, we will develop a protocol to determine the localization, activity, and structure of FMRP granule-associated ribosomes in iPSCs. This aim will establish a workflow and reveal how ribosome localization and activity are regulated by FMRP in neurites. In aim 2, we will determine the localization, activity and structures of ribosomes associated with nRNAgs and FXGs. This aim will reveal how ribosome inactivation differs between granule types. More broadly, these investigations will lay the foundation for mechanistic studies aimed at understanding how translation contributes to human disease in a location-specific manner. Our work will provide structural insights into translational regulation, a fundamental process for proper neuron function. Furthermore, it will enable the application of this analysis to patient-derived human iPSC models of neurodevelopmental diseases, aligning with the missions of the National Institute of Neurological Disorders and Stroke.
NSF Awards · FY 2024 · 2024-06
Mobile devices, such as smartphones and tablets, embed multiple processors to efficiently carry different types of computation. In such systems, applications running on different processors store their data on a single shared memory. This project uncovers certain security vulnerabilities that mobile systems with shared memories possess. Leveraging these vulnerabilities, a malicious party could circumvent existing protection mechanisms and extract sensitive information by monitoring data access patterns. The research will develop a framework to better understand potential attacks and investigate several protection mechanisms. Broader comprehension and mitigation of these attacks hold crucial importance in protecting intellectual property and user privacy in mobile devices. The award contributes to enabling a more secure operation of billions of mobile devices used daily around the globe. This project investigates a critical side-channel leakage mechanism based on the memory-access contention occurring when multiple applications execute together in a multi-processor system with shared memory. An adversary could exploit this leakage to build attacks and extract intellectual property, such as the hyper-parameters of neural networks used in biometric authentication, without requiring special privileges or comprised hardware. This project builds upon an attacker framework to extract unique memory-contention-based signatures of victim applications. New profiling and analysis techniques are developed to capture non-linear memory access characteristics of machine learning and artificial intelligence workloads. The signatures are then used to create reverse-engineering, information extraction and denial-of-service based attacks. Finally, various countermeasures at architecture- and system-level are developed against the new attacks. The research team investigates the security, performance, area, and energy implications of new memory controller scheduling policies and randomization-based solutions. This project unveils a previously overlooked class of cybersecurity threats with financial and privacy-related impacts. The awareness and mitigation of the new security issues strengthen the trustworthy operation of billions of mobile devices. 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 · 2024-04
Distributed systems are the backbone of modern computing. However, they are complicated and prone to bugs due to their combinatorially large state-spaces, and node and network failures. Recent occurrences of data, currency and service loss have shown that reliability of distributed systems remains elusive. The inherent complication is faced by not only protocol and system designers that provide interfaces but even distributed application programmers that use these interfaces. This project addresses programmer productivity and reliability of distributed systems that spans both the client applications and the supporting distributed middleware. This project includes both novel automatic synthesis techniques for client applications and novel verification techniques for distributed middleware. Distributed stores provide a spectrum of consistency choices that impose a dilemma for clients between correctness, responsiveness and availability. Given the high-level integrity properties of the application, this project automatically decides the minimum required coordination that guarantees integrity and convergence and automatically synthesizes protocols for replicated objects. The reliability of these applications is crucially dependent on the correctness of the underlying middleware of subtle protocols such as broadcast and consensus. The middleware is classically designed as stacks of layers, and its correctness is often stated compositionally as intuitive arguments on temporal precedence of the events exchanged between each layer and its sub-layers. This project builds a development and verification framework in a proof assistant to design a mechanically verified middleware stack. The framework is based on a compositional and temporal program logic so that the proofs match the intuitive arguments. 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 · 2024-02
ABSTRACT A major challenge for the cancer genomics community is determining which somatic mutations are contributing to tumorigenesis, which are “passenger” (neutral) mutations, and which mutations will inform personalized treatment decisions. Unfortunately, most functional studies of cancer mutations have largely ignored the impact of altered RNA processing even though this alteration is widespread in cancer, and is a mechanism of both oncogenesis and therapeutic resistance. We hypothesize that we are missing critical information about cancer gene alterations when not considering isoform-specific functions and this is likely to affect cancer treatment. Given the breadth in the lack of understanding of isoform-specific cancer gene function, high-throughput approaches are vitally needed to identify cancer gene isoform variants and functionally characterize their effect on cancer development and treatment. Aim 1 of this study will generate a compendium of human pan-cancer gene isoform variants by performing long-read transcriptome sequencing on a panel of cancer cell lines and primary lung tumors to build a comprehensive set of allele-specific, full-length transcript isoforms. Aim 2 will identify gene isoform variants associated with resistance or variable response to targeted therapies in patient-derived specimens and xenograft models. Aim 3 will perform high-throughput in vitro and in vivo functional characterization of these isoforms driving oncogenesis and drug resistance with and without somatic mutation to identify isoform-specific variant function. All of these aims will focus on genes in the RAS-RTK pathway since this is the most frequently mutated oncogenic pathway and contains many targetable genes. Completion of this study will revolutionize our understanding of isoform-specific functions of cancer genes and their contribution to oncogenesis and cancer treatment. Our approach will provide the cancer research community with a much-needed framework and methodology for other cancer studies and will provide critical insight into mechanisms of tumor response and resistance to cancer therapies.