2005 — 2007 |
Sears, Karen E |
F32Activity Code Description: To provide postdoctoral research training to individuals to broaden their scientific background and extend their potential for research in specified health-related areas. |
Genetic and Morphologic Basis of Bat Wing Development @ University of Colorado Denver
DESCRIPTION (provided by applicant): The sudden appearance of bats in the fossil record (approximately 50 million years ago) suggests that the evolution of the morphological specializations of bats for powered flight (i.e., elongation of the forelimb phalanges and reduction of the ulna) occurred very rapidly. This study tests the hypothesis that changes in limb morphology, as seen in the rapid evolution of bats, arise from changes in the temporal and spatial expression of a few key regulators of limb development. To test this hypothesis, the molecular and morphological patterning of the specialized limbs of a bat (Carollia perspicillata) will be compared with those of a mouse (Mus musculus) that closely resemble the limbs of the pre-flight bat ancestor. By illustrating the morphological and molecular basis of the evolution of the bat wing, this study will provide a better understanding of the relationship between gene expression patterns and the resultant morphologies and expand our knowledge of the natural variation of the roles of these genes. In addition, understanding the normal roles of genes that also play a role in abnormal developmental events such as cancer (i.e., Ihh and BMP) will provide a knowledge base for additional healthcare-related biomedical research.
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0.964 |
2013 — 2016 |
Zhong, Sheng (co-PI) [⬀] Sears, Karen |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Collaborative Research: Genetic Determinants of Mammalianllimb Biodiversity @ University of Illinois At Urbana-Champaign
A major goal of biology is to identify the processes that shape the evolution of form and structure. To pursue this important goal, this project will take an innovative, comparative approach to investigate how evolutionary changes during limb development (the process by which the limb forms) contribute to the generation of the divergent limbs of three mammals: bats, opossums, and mice. The mammal limb is an ideal system with which to pursue this goal because the way that a mammal feeds, moves and behaves is dependent upon the form of its limbs. As such, from the wings of bats to the flippers of whales to the hooves of horses, the diversification of the mammal limb has been crucial to the ecological and evolutionary success of the group. Through use of traditional and next generation genetic analyses, this project will identify the specific changes in gene expression (e.g., when genes are turned on and off, and at what levels) that initiate and drive the divergence of limb form among mammalian species. This knowledge will vertically advance our understanding of how the process of development constrains and facilitates the evolution of certain limb forms, and thereby impacts mammalian evolution. Furthermore, as humans are mammals, this project will directly advance our understanding of the processes that have shaped our own evolutionary history.
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0.915 |
2014 — 2019 |
Sears, Karen |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Dimensions: Collaborative Research: Discovering Genomic and Developmental Mechanisms That Underlie Sensory Innovations Critical to Adaptive Diversification @ University of California-Los Angeles
All animals must sense their environment and other organisms to find food, avoid threats, and find partners. The ability of some individuals to locate food and mates more effectively than others can open opportunities for them to leave many more descendants. And yet, multiple advanced sensory systems seldom evolve in the same species despite the advantages they may confer, suggesting there are physical limits to developing several specialized senses. This project focuses on a diverse group of tropical bats in which various species evolved acute, specialized hearing, supersensitive eyes, the ability to smell subtle plant chemicals, or highly developed vomeronasal systems (thought to contribute to mating and social hierarchy). This project will compare approximately 2000 genes involved in vision, hearing, olfaction and the vomeronasal system in more than 150 bat species. To find out how some of these genes contribute to developing distinct sensory systems, their actions will be studied in the lab. This research will uncover the role of specific genes in the acquisition of specialized senses, test whether the size of the head limits the number of specialized sensory structures a species can have, and discover how sensory adaptations contribute to the diversity of species through time.
This project will uncover the evolution of genes and structures of the auditory, visual, and olfactory and vomeronasal systems in a large superfamily of bats characterized by diverse sensory adaptations associated with specific diets. Analyses of gene evolution will be used to test the hypothesis that sensory innovations arise through gene duplication and positive selection. Measurements of gene expression from tissues collected in the field, and experiments to express key bat genes in developing embryos will be used to elucidate how genes shape adaptive sensory structures. Comparative analyses of detailed measurements of the size of sensory structures will evaluate trade-offs between sensory systems and the way these may limit diversity of diets or species. State-of-the art methods to quantify relationships between gene and trait evolution and species diversity will be used to discover the impact of sensory adaptation on species diversity through time. This research will illuminate the main biological forces in the genome, during embryonic development, and in anatomical structures that contribute to the success of species in adapting to their ever-challenging environment.
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0.915 |
2014 — 2016 |
Urban, Daniel Sears, Karen |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Dissertation Research: Mechanisms of Mammalian Middle Ear Ossicle Transition From the Reptilian Jaw Joint @ University of Illinois At Urbana-Champaign
The transition from reptile to mammal was one of the most important events in leading to the eventual evolution of humans. This transition is characterized by many changes, one of the most important is the evolution of the mammalian middle ear. The goal of this project is to investigate the developmental basis of the evolution of the mammalian middle ear, using an opossum species as a model organism. Because opossum are primitive mammals, they can provide significant insights into mammalian evolution, and the improved understanding of ear development that this project will generate has the potential to positively impact human health. This project will also serve as a foundation for the STEM training of several undergraduates and for community outreach events geared toward K-12 students. Results of this project are also being incorporated into a three-part PBS documentary based upon Neil Shubin's best-selling book, Your Inner Fish.
The reptilian jaw consists of multiple bones, while there is only a single bone in the reptile middle ear. Conversely, the mammalian jaw consists of a single bone, while there are multiple bones in the mammal middle ear. It has been shown, via paleontology and embryology, that the extra bones in the mammalian middle ear originated from the extra bones in the reptilian jaw. Separation from the jaw would allow more flexibility in the evolution of the middle ear elements, resulting in increased hearing sensitivity and amplified frequency range. The middle ear changes observed in the transition from reptiles to mammals in the fossil record also occur during development in opossum. Opossum are born with a middle ear similar to reptiles, but in adults the middle ear is mammalian, providing a unique opportunity to study the evolutionary development of mammalian middle ear bones in an currently living organism rather than with fossils. The project is based on a detailed characterization of the transition using micro-computed tomography scans to create three-dimensional images at five day intervals, beginning at birth, and studying the cellular processes underlying the transition by cryosectioning at the noted stages, followed by immunohistochemistry for cell proliferation and apoptosis. The project will uncover the genes responsible for the transition using in situ hybridization and RNA sequencing. Alterations in the timing of expression and concentration of particular genes (e.g., TGTbr2 and Eya1) are expected to be correlated with the separation of Meckel's cartilage and functional changes in the ossicles. The research will determine if the active genes in opossum are also expressed in the middle ear region of placental mammals. The project will compare the transition that occurs during opossum development to that observed in fossil record leading to early mammal lineages.
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0.915 |
2016 — 2017 |
Sears, Karen E |
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.) |
Developing Techniques to Generate the First Transgenic Opossums @ University of California Los Angeles
Project Summary The grey short-tailed opossum (Monodelphis domestica) is a small pouchless South American marsupial is a widely used model system for research into biomedicine and evolution. It is born prematurely, with well-developed forelimbs that permit it to climb to the mother's teat to complete its development. The hindlimbs, intervertebral disc, and a number of other organ systems are at a rudimentary stage of formation at birth. Because of the disparity in limb formation at birth, the opossum has long been used as a `natural' mutant for the study of limb formation. A number of evolutionary comparisons have been made between placental and marsupial mammals with this study system. In addition, the opossum has also been used in cancer research (particularly melanoma), studies of high cholesterol, spinal cord regeneration, wound healing, and birth defects (particularly thalidomide and retinoic acid teratogenesis), to name just a few. A number of resources have been developed for its husbandry, embryo collection, immunohistochemistry, in situ hybridization, and tissue culture. Its genome was also recently sequenced and organ-specific transcriptomes generated by RNA-Seq analysis. The opossum is also small-sized, fairly easy to raise in a laboratory setting, and relatively docile. Despite all these advantages, the main drawback to the marsupial model is a lack of transgenic or knockout animals. Transgenic mice have been available for decades, and become easier to make as technology improves. In addition, transgenic and other engineered mutants are becoming common for rats and other domestic mammals, particularly farm animals and non- human primates. Previous attempts to generate a transgenic opossum have had limited success. We propose to generate the first transgenic opossums based on a method that has been used to great success in other mammals, rodents especially. Spermatogonial stem cells (SSCs) from opossums will be harvested from the testes, cultured and expanded in vitro, transformed with a reporter-carrying construct, and transplanted into donor male opossums. If successful, this work will not only provide valuable comparisons of marsupial vs. placental mammal SSC biology, but will build the foundation for mutagenesis and transgenesis in an opossum model. Theoretically, it will be possible to utilize the increasingly popular CRISPR/Cas9 system in opossum SSCs and transplant them to donor males. For the many users of marsupial models, the availability of a transgenic marsupial model would be a critical addition to a growing toolkit. This proposal will be a proof-of-concept for the generation of opossums expressing exogenous DNA.
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1 |
2020 — 2023 |
Sears, Karen |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Collaborative Research: Understanding the Role of Developmental Bias in the Morphological Diversification of Bat Molars @ University of California-Los Angeles
The evolution of animal form has been uneven, radiating in fits and starts, and exploring some forms but not others. Why this pattern exists has long been a fundamental question in biology. One possible explanation can be found in the very nature of the way that animals grow from an egg into an adult, i.e., in their development. The genes that control animal development interact in networks. Some genes in these networks interact with many other genes, while others are more peripheral and isolated. This project tests the hypothesis that most evolution in animal form occurs through changes in peripheral network components, and in the aspects of form that those peripheral components make, while central genes and their associated forms are conserved among species. To test this hypothesis, this project investigates the patterns and drivers of tooth evolution in an ecologically diverse animal group, noctilionoid bats. This project is expected to be among the first to characterize the organization of the gene networks that control animal form, and the impact that this organization has on the way evolution proceeds. This project is therefore expected to illuminate mechanisms that have shaped the evolution of animals over the history of life on earth. This project will also directly increase participation of students from underrepresented groups (URMs) in research and contribute to public education. These goals will be achieved by involving URM undergraduates from Puerto Rico in project research, training postdoctoral scientists in URM mentorship, and showcasing project results at the Burke Museum.
This project?s goal is to characterize and model the evolution of developmental GRN modules and resulting morphologies, using the radiation of noctilionoid bats and their molars as a model system. This project's central hypothesis is that a conserved core module of the molar GRN controls the initial formation of molar traits that are conserved across species, with evolutionary modification of network sub-modules leading to interspecific morphological variation. To test this, two aims will be completed. In Aim 1, the team will quantify morphology of developing lower first molars (m1) in representative noctilionoids, and adult m1s across all extant noctilionoid genera. Data will be used to reconstruct the development and evolution of noctilionoid m1 morphology, and identify conserved and variable traits over developmental and evolutionary time. In Aim 2, the team will map gene expression over m1 development in representative noctilionoids, functionally test the ability of observed expression differences in key molar developmental pathways to generate variable m1 morphologies, reconstruct GRN modules for bat m1s in computational space, and link GRN modules to m1 morphological diversity. Using data from both aims, the team will also use machine-learning techniques to reverse-engineer a computational model that will predict m1 phenotypes resulting from variation in developmental modules. Through this research, this project will characterize the role of developmental biases in morphological evolution within an adaptive radiation, functionally link shifts in gene expression to the evolution of morphology among closely related species, and generate a predictive model for morphological evolution across a hyper-diverse mammal group
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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0.915 |