2005 — 2008 |
Dellaporta, Stephen (co-PI) [⬀] Powell, Jeffrey (co-PI) [⬀] Caccone, Adalgisa Donoghue, Michael (co-PI) [⬀] Yoder, Anne (co-PI) [⬀] |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
A High-Throughput Dna Analyzer For Comparative Population Genomics
This award provides support to enable the purchase of a high throughput DNA analyzer, thermocycler and robotic workstation to be placed in a core microchemistry facility where it will be used and maintained by facility staff. This set of equipment is now a mainstay of research programs requiring high throughput DNA sequencing, microsatellite analysis, and single-nuculeotide polymorphism surveys. Investigators whose research and training efforts require use of the equipment will be charged using a set fee for service schedule. Placement of such equipment in a core facility fosters communication among different research groups who use the equipment leading to the sharing of ideas, information, and technical innovations. It also maximizes the use of the equipment by making the equipment available to a large number of other users from different disciplines and departments across campus. The equipment will allow the PI and her colleagues to expand their capacity for population-level analysis via enhancement of fragment analysis (e.g., microsatellite DNA), and more importantly, via single nucleotide polymorphism survey. The requested equipment will be housed in the Yale Institute for Biospheric Studies - Molecular Systematics and Conservation Genetic laboratory (YIBS - MSCG) which trains students in molecular techniques applied to environmental and organismal level questions. Since its inception, the YIBS - MSCG has trained students via research rotations, formal laboratory courses, dedicated seminars, and workshops. The equipment will enhance training by allowing students to obtain genetic information from large data sets in a time frame that is appropriate to their academic schedules, and do so within the budget available for training. It will also expose them early in their scientific life to state of the art equipment. The equipment is also expected to impact joint efforts of YIBS - MSCG with the Yale Peabody Museum in a science literacy partnership with the public school district of New Haven. Via this program, middle schools characterized by underachieving minority students from low-income families are targeted for educational outreach. The partnership, begun two years ago, plans to integrate the YIBS-MSCG laboratory as a means for offering additional opportunities for learning and hands-on training.
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2009 |
Caccone, Adalgisa |
S10Activity Code Description: To make available to institutions with a high concentration of NIH extramural research awards, research instruments which will be used on a shared basis. |
High-Throughput Genetic Analyzer Upgrade For Comparative Population Genomics
DESCRIPTION (provided by applicant): We request funds to purchase multiple instruments that will increase the throughput capacity of the DNA Analysis Facility on Science Hill (DAFSH) at Yale University. Currently DAFSH is functioning as a medium-throughput, fee-for-service and non-profit Core Facility offering DNA Sequencing and multiple Fragment Analysis services to Yale Researchers and the broader scientific community. Upgrading our equipment will allow us to effectively serve increasing demands from several research laboratories with NIH funded projects. This group of scientists'works within a diverse array of health related fields with well-established track records using DNA based approaches. Although there is a larger DNA Sequencing core facility on campus, DAFSH provides services, such as microsatellite analysis, which are not available in any other core facility at Yale or in the surrounding area, catering to small and medium sized laboratories. The infrastructure for successfully managing current equipment is well established with experienced personnel dedicated to its operation and maintenance ensuring its longevity. The facility is directed by an NIH sponsored investigator and it is located within her laboratory, which serves also as a research and training facility sponsored by the Yale Institute for Biospheric Studies (YIBS). This ensures on-site experienced help that provides troubleshooting and training of new users, if needed. The Yale Shared Science Service Branch, which oversees all business matters of Science Departments, provides administrative and financial assistance. Currently the limiting factor in our Core Facility is the processing speed and throughput capacity of the ABI 3730 DNA Analyzer. Upgrading the Facility offers several practical advantages to all of our major and minor users, including decreased rates and faster delivery of data. By promoting access to the equipment to additional Yale and non-Yale research groups we enhance cost effectiveness, reducing idle time and avoiding wasted consumables. This in turn allows us to reduce rates and make the services available to users that could otherwise not afford it. The increased capacity we seek to obtain by acquiring the requested equipment will enable this group of NIH investigators to gain more data on their research projects than with the resources presently available to each of them. Simply put, it ensures a better return in terms of what each researcher can achieve with their NIH funds. PUBLIC HEALTH RELEVANCE: By processing samples in a centralized non-profit core facility the major users can collect quality data at a cheaper rate than possible if using either commercial companies or doing the DNA analyses on their own. This reduces the economical and labor commitments of investigators, which can concentrate on less technical aspects of their public health related projects. The fact that the facility employs and trains several undergraduates also has a long-lasting impact in health related fields, since it exposes future generations of NIH researchers to DNA based genomic research in health related areas.
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2011 — 2012 |
Aksoy, Serap (co-PI) [⬀] Caccone, Adalgisa |
R21Activity Code Description: To encourage the development of new research activities in categorical program areas. (Support generally is restricted in level of support and in time.) |
Next Generation Sequencing of East African Trypanosomes to Expand the Molecular E
DESCRIPTION (provided by applicant): Human African trypanosomiasis, also known as sleeping sickness, is a zoonotic disease affecting thousands of people across sub-Saharan Africa and periodic epidemics have caused significant social and economic disruption. The trypanosome responsible for sleeping sickness is morphologically indistinguishable from closely related parasites found in animals, leading to confusion regarding the origins of human disease outbreaks. This project seeks to improve the tools available for understanding the epidemiology of this neglected disease. The immediate aims are to develop a robust and broadly applicable panel of genetic markers and to validate these in a pilot study in Uganda, a disease-endemic country currently experiencing a severe epidemic. This project will employ next-generation sequencing of multiple trypanosome genomes, selected to encompass the complicated evolutionary relationships observed among trypanosomes in preliminary studies. The genetic polymorphisms identified from genome comparisons will be evaluated for their ability to resolve fine scale population structure and to distinguish between human-infective and animal-restricted parasites in the Ugandan disease focus. In the longer term, the markers developed in this project will provide a foundation for cataloguing the full diversity of trypanosomes in nature, for identifying the pool of trypanosomes that are most relevant for human disease, and for characterizing the relationships among trypanosome populations distributed across eastern Africa. In addition, comparisons among the genomes of animal-restricted and human-disease causing trypanosomes will provide insight into the functional genetic differences conferring human infectivity. PUBLIC HEALTH RELEVANCE: This project, which seeks to develop new molecular markers for understanding human sleeping sickness in eastern sub-Saharan Africa, will provide a universal diagnostic platform for monitoring parasites found in animal reservoirs with respect to important traits such as human infectivity, disease severity and drug resistance. In addition, this project will enable future population genetic studies aimed at identifying major social, evolutionary and ecological forces influencing disease transmission. This information will help to identify optimal methods for preventing and controlling disease outbreaks.
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2013 — 2016 |
Post, David [⬀] Caccone, Adalgisa |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Collaborative Research: Rapid: Using River Restoration to Test the Ecological and Evolutionary Effects of Secondary Contact
In many aquatic ecosystems, dams have isolated fish populations for decades to centuries and the isolated populations have diverged both morphologically and genetically. Secondary contact between previously isolated populations will occur as these dams are removed or restoration efforts restore spatial connectivity. This RAPID project will examine the ecological and evolutionary consequences of the initial stages of secondary contact; restoration of river connectivity will soon allow secondary contact between anadromous alewife populations and landlocked populations in Rogers Lake, Connecticut. Divergence in morphology, foraging behavior, and migration has altered the ecological role of these two alewife life history forms over the past 250-350 years. Research will examine the inbreeding between anadromous and landlocked alewife using genetic markers to track introgression. It will document changes in food web structure, nutrient loading, and habitat and resource use by alewife at the initiation of secondary contact. By documenting these important direct and indirect effects of initial contact between anadromous and landlocked populations, the project will significantly advance our understanding of a process that is fundamental to the origin and maintenance of biodiversity.
Although anadromous alewives are a critical resource in freshwater and marine habitats and a federally listed species of conservation concern, landlocked alewives are invasive across their range. The investigators will continue work with local lake associations, land trusts and the regional conservation and management community to aid anadromous alewife restoration efforts by contributing results from this study. They will take advantage of an NIH-funded Yale program to recruit under-represented minority undergraduate students to the project, and will train them in the broader scientific context of the research, research methods, data analysis, and written and oral project reports. Outreach talks to the general public, education programs targeting underrepresented minority groups, interactive displays, and digital outreach via internet and social media are also planned.
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2014 — 2015 |
Walter, Katharine Caccone, Adalgisa Diuk-Wasser, Maria [⬀] |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Dissertation Research: Invasion Phylogeography of Borrelia Burgdorferi, a Tick-Borne Pathogen
Tick-borne diseases pose a significant and growing global health burden due to the expanding range of tick vectors, reservoir hosts, and pathogens, as well as a suite of other environmental pressures. Lyme disease is the most prevalent tick-borne disease in the US and the vast majority of cases occur in the Northeast. Over the past forty years, it has rapidly spread from southern New England through Maine as well as through the Upper Midwest. Despite its epidemiological importance, the source and trajectory of the ongoing invasion remains poorly described. This project harnesses the tools of next generation sequencing to reconstruct the evolutionary history of the Lyme disease bacteria, Borrelia burgdorferi. Surveying the genomic diversity of the pathogen will allow us to infer the probable origin of invasion and pathways of spread and will inform a better understanding of the environmental or ecological factors driving the emergence.
Resolving the invasion history of B. burgdorferi will inform models of continued spatial spread and targeted control measures for this important human pathogen. Further, this project will support the research of a team of three female scientists and the training of at least four undergraduate assistants, including women and minorities, and several high school students in field ecology, epidemiology, and evolutionary genomics techniques.
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2014 — 2018 |
Aksoy, Serap [⬀] Caccone, Adalgisa |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Evolutionary Genetics of Tsetse and Its Symbionts
DESCRIPTION (provided by applicant): African trypanosomiasis impacts both human and animal health in Sub-Saharan Africa. Uganda is the only country that has both forms of the human African trypanosomiasis (HAT): Trypanosoma brucei gambiense (Tbg) in the north-west and Trypanosoma brucei rhodesiense (Tbr) in the south-east. Tbr cases have been migrating from their traditional foci in the south to central Uganda, with the two disease belts feared to merge in northern Uganda. This interdisciplinary project focuses on northern Uganda to understand HAT transmission dynamics and risk of Tbr and Tbg disease merger. Our findings will provide fundamental knowledge on the role of the vector in HAT epidemiology, and provide practical information to inform the development and implementation of effective control strategies. We propose five integrated aims to: 1) Analyze the genomic variation in Gff, its associated microbiome and parasite (Trypanosoma) using a multispecies SNP chip, 2) Characterize the expression and genetic variations of the Trypanosoma-resistance candidate genes in different Gff population groups, 3) Discover gene-environment associations and impacts of climate change on Ugandan Gff, 4) Understand genetic as well as microbiome contributions for differentiation of Gff populations and 5) Assess the impact of Gff dispersal on the effectiveness and cost-effectiveness of vector control for reducing trypanosomiasis burden. Our studies will produce 1) fundamental information on host-parasite interactions that will predict the potential risk of disease merger and its epidemiological consequences, 2) suitability maps for Gff based on genetic and environmental data to better plan and operate vector control activities, 3) candidate genes on parasite-resistance, environmental adaptations that can be used in downstream genetic control methods and 4) predictions on the most effective and cost-effective control methods for HAT.
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2015 — 2016 |
Ben Mamoun, Choukri Caccone, Adalgisa Diuk-Wasser, Maria Ana (co-PI) [⬀] |
R21Activity Code Description: To encourage the development of new research activities in categorical program areas. (Support generally is restricted in level of support and in time.) |
Probing the Natural Genomic Diversity of Babesia Microti
DESCRIPTION (provided by applicant): Human babesiosis, a malaria-like febrile illness is an emerging tick-borne disease caused by Babesia microti (Bm), which is maintained in a similar enzootic cycle as Borrelia burgdorferi, the Lyme disease agent. Bm is the most common transfusion-transmitted pathogen in the United States and results in a ~20% mortality rate in transfusion recipients and other immunocompromised hosts. A critical bottleneck for epidemiological and evolutionary studies of this and other vector-borne pathogens has been the difficulty in obtaining sufficient numbers of whole genome sequences (WGS) of pathogens distributed across their geographic and host distribution. The only means to capture the complete diversity spectrum of vector-borne pathogens is to sequence directly from Ixodes scapularis nymphal ticks, because nymphs feed as larvae on all potential reservoir hosts. However, because of the small genomic size of the pathogen relative to the host, and their often low copy number in mixed DNA samples, the pathogen's genome signal is swamped by exogenous DNA, rendering next generation shotgun sequencing for these templates inefficient and costly. A novel approach is required to provide the epidemiological and clinical communities with genomic resources for a variety of downstream applications. We propose a novel culture-independent method for deriving whole genome sequences for vector-borne and zoonotic pathogens, allowing pathogen genomic variation to be studied directly from tick and human blood samples and thus enabling analyses at an unprecedented resolution. Specifically, we will adapt DNA target capture techniques, previously used in human genomic analyses, to probe the genomic diversity of B. microti in 120 strains sampled directly from field collected I. scapularis ticks, as well as 20 strains from human blood. This approach has never before been applied to vector-borne and zoonotic pathogens. Using these genomic resources, we will analyze the patterns of standing B. microti genetic diversity and characterize patterns of B. microti spread in the northeastern United States. This exploratory analysis will elucidate the degree of B. microti spatial population structure, identify the origin of human infective strains, and enable us to reconstruct B. microti invasion history across the Northeast. Together with understanding of the pathogen population structure, we will define the pool of parasites that can give rise to human disease, thereby contributing to future disease surveillance and control strategies. These baseline data will enable future epidemiological studies and clinical investigations aimed at understanding the mechanisms underlying human infectivity and provide the basis for parasite diagnostics relative to lineage-specific variation in important traits such as infectivity and disease severity.
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2016 — 2020 |
Post, David [⬀] Caccone, Adalgisa |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Collaborative Research: Ecological and Evolutionary Dynamics of Secondary Contact
Rivers and streams across the country are being restored to their original flow patterns by the removal of dams, many of which were constructed centuries ago to provide energy for small mills that formed the basis of colonial economies. This project takes advantage of planned dam removals that will connect fish populations that have been separated for nearly four centuries, in order to study the ecological and evolutionary consequences of secondary contact between these recently divergent fish populations, which may interbreed but also may compete. Results from this work will contribute to the conservation and management of migratory alewife fish, a critical resource in coastal freshwater and marine habitats and the focus of intensive restoration and conservation efforts. Researchers will work collaboratively with state managers, the Connecticut Department of Energy and Environmental Protection, lake associations, and land trusts to determine the consequences of restoring migratory populations, provide information vital to alewife recovery, and educate local communities on the consequences of river restoration. The project will train a postdoctoral researcher along with graduate and undergraduate students in an interdisciplinary project that relies on advanced genetics techniques, field sampling, and manipulative field and laboratory experiments. An existing program at Yale University will support involvement of underrepresented minority undergraduate students in summer research. Training will include the broader scientific context of the research, research methods, data analysis, written and oral project reports, and direct involvement with the public to present the societal benefits of the research.
This project takes advantage of whole-lake restoration projects to understand the ecological and evolutionary dynamics of secondary contact between recently diverged lineages of alewife. Isolation caused by construction of dams has resulted in two divergent alewife life history forms: the ancestral anadromous form that moves between lakes and the coastal ocean and a landlocked form that is resident in lakes. This project will combine advanced genomics, small-scale experiments, and whole-lake observations and experiments to document and understand the consequences of secondary contact, when dam removal allows reintroduction of anadromous alewife into lakes that contain the land-locked form. Close collaboration with the state agency that removes dams will allow the investigators to study secondary contact from its initiation. The project addresses three stages in response to secondary contact: rapid ecological change in planktonic communities and nutrient flux, rapid evolutionary responses in invertebrate populations in response to novel ecological conditions, and interactions between the two alewife morphs that may result in hybridization and, over the longer-term, alewife evolution and local adaptation. The first of these responses - ecological changes in lacustrine communities - is essential in order to interpret the evolutionary changes that result. The project is unique in its ability to capture the consequences of secondary contact on both time scales. Results will provide rare insight into feedbacks between ecological and evolutionary processes in field populations following secondary contact with important implications for ecosystem function and the maintenance of biodiversity in restored ecosystems.
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2018 — 2021 |
Armbruster, Peter (co-PI) [⬀] Caccone, Adalgisa |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Population Genomics of a Globally Distributed Arbovirus Vector, Aedes Albopictus
Project Summary Aedes albopictus, is an aggressive human-biting mosquito and a competent vector of at least 22 arboviruses, including dengue, chikungunya, and Zika. Ae. albopictus represents a geographically extensive public health risk because of its ability to withstand cold temperatures which allow it to spread and establish from the native tropical regions to temperate localities. This ability to rapidly adapt to different temperature regimes represents a serious public health concern, especially in heavily populated urban areas of the U.S. where Ae. albopictus can occur at high densities. Lack of vaccines and drug treatments for most arboviruses makes vector control the most effective strategy for curbing disease spread. Our first goal in the proposed research is to develop a new powerful genetic tool for Ae. albopictus, a SNP chip to efficiently genotype tens of thousands of loci. This tool will address a longstanding knowledge gap due to the lack of high-resolution genetic markers for Ae. albopictus, and will be useful for a wide range of research topics from ecology to vector competence. In addition, a recent initiative by Verily Life Sciences (subsidiary of Google) to sequence 1000 Ae. albopictus will provide another rich source of data for our proposed work. In the current proposal we will: 1) Perform genetic surveys of worldwide field populations to reconstruct the species history and to allow rapid identification of the geographic origin(s) or current and future invasions (worldwide scale); 2) Understand the demographic parameters associated with range expansion on two previously identified and studied latitudinal transects from tropical to temperate areas in the native and invasive range (local scale); 3) Construct a publicly accessible standardized database of genetic variation of the species that can be used to trace future changes in this invasive species range; 4) Collect phenotypic data on diapause incidence from these samples and use the SNPs to identify genomic regions associated with diapause incidence to provide novel tools for vector control by disrupting this key trait linked to climatic adaptation. Results from this research will provide fundamental knowledge on the population dynamics of this important vector in its native and invasive habitats. The data will also provide practical information to help in the development and implementation of effective monitoring and control strategies.
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2021 — 2024 |
Caccone, Adalgisa |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Collaborative Research: Adaptive and Nonadaptive Mechanisms of Phenotypic Evolution in Response to Urbanization
Over half of the world?s population lives in cities, and urban areas are among the fastest growing ecosystems on Earth. Urbanization causes dramatic environmental change, from the conversion of natural areas to buildings and roads, to increased air, water, light, and noise pollution. Urbanization often reduces biodiversity, but it can also affect the way organisms evolve. Organisms that thrive in cities commonly differ in their morphology, behavior, and physiology from populations of the same species in rural areas. How do these differences arise? This project?s focus is one of the most common and visible animals in cities in the United States and abroad: gray squirrels. Gray squirrels provide an ideal model system for exploring the different ways urbanization affects evolution. Gray squirrels have two common coat colors ? gray and melanic ? that are determined by a single gene. The melanic form used to be common in much of the northeastern United States, but today it is abundant primarily in cities. Why did melanic squirrels decline in rural forests but persist in cities? Results from this project will shed light on fundamental questions about how urbanization affects the way organisms evolve, that is, the degree to which evolutionary change in cities and surrounding rural areas is due to natural selection, chance, or a combination of both. The project will engage thousands of citizen scientists and students in recording observations of squirrel coat colors and collectively measuring in their backyards how evolution is shaped by urbanization. The research will address longstanding questions about urban evolution specifically and evolutionary biology more generally and help guide efforts to enhance biodiversity and human well-being in cities.
The research will integrate demographic and genomic approaches across 10 replicate cities to understand how melanism evolved in response to urbanization. First, spatial variation in melanism will be characterized in each city to test whether melanism consistently declines from the urban core into rural forests. Second, genomic tools will be used to investigate the degree to which changes in melanism from urban to rural areas are driven by adaptive natural selection versus nonadaptive processes, including chance introductions and dispersal through the urban environment. Third, experiments will be conducted to understand the causes of natural selection, testing the idea that urbanization alters vulnerability of different morphs to different sources of mortality in cities and rural forests. Citizen scientists will be engaged in an online experiment to measure the visibility of each morph in urban and rural environments, and predation rates on the morphs will be compared in each environment.
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.
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