2007 — 2014 |
Goodisman, Michael Yi, Soojin |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Evolution of Phenotype-Specific Genes in Social Insects @ Georgia Tech Research Corporation
Organisms can alter their physical form by varying the genes that they activate. However, the evolutionary forces that shape genes activated in different forms remain unclear. The objective of this research program is to gain a greater understanding of how natural selection affects genes that are differentially activated between forms. Goodisman and Yi will use social insects as models for investigating this question. They will use molecular genetic techniques to detect genes differentially activated between different social insect castes and sexes. They will then use evolutionary analyses to (1) test the effect of caste-specific gene activation on molecular evolution and (2) test the effect of differing mating system on the evolution of sex-specific genes.
This research is of broad scientific importance because it advances our understanding of the evolution of genes that lead to the development of different organismal forms. Goodisman and Yi will uncover how genes that are expressed under distinct environmental conditions evolve. Their studies will also add to our knowledge of the evolution of sex differences. Finally, this research increases our understanding of the molecular basis underlying the success of social insects, which are among the most ecologically successful and economically important of animal species.
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0.93 |
2010 — 2014 |
Goodisman, Michael Yi, Soojin |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Collaborative Research: Epigenetic Gene Regulation in the Social Bee Apis Mellifera @ Georgia Tech Research Corporation
Intellectual Merit: Every cell in an organism carries the same sets of genes. However different cells perform different functions because only subsets of genes are activated in each cell. One way that cells activate specific sets of genes is by chemically modifying particular pieces of DNA. This project investigates how one such modification, DNA methylation, affects development in the honeybee. Honeybees are well-known social insects and represent important species for studying DNA methylation because of their ecological and economic importance. In addition, the differentiation of honeybee castes represents one of the most spectacular examples of developmental plasticity: queens and workers arise from the same genes through differential gene activation mediated by DNA methylation. Consequently, determining how DNA methylation affects development in honeybees would help link specific molecular mechanisms to the production of different developmental forms and provide insight into the factors affecting social behavior.
Broader Impacts: This project will result in several broader impacts to society. For example, undergraduate and graduate students will be trained in integrative multidisciplinary research. Research findings will also be implemented in university classes and laboratories. Moreover, research findings will be disseminated through popular press and scientific meetings thereby increasing scientific literacy. Finally, because honeybees are critical species for pollinating crops, these studies will contribute to improving agricultural outcomes in the United States.
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0.93 |
2014 — 2015 |
Maney, Donna L [⬀] Yi, Soojin |
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.) |
Resource Development For a New Model of Social Threat Response
DESCRIPTION (provided by applicant): The underlying genetic basis of variation in social behavior is of intense interest, yet only a handful of genes have been linked to specific social behaviors in vertebrates. Thus, there is a strong need to identify populations, human or otherwise, in which there is clear linkage between genes and social behavior. In the proposed project, resources will be developed to take advantage of a uniquely suited model, the white-throated sparrow. Males and females of this abundant North American songbird occur in two plumage morphs that differ with respect to the presence of a chromosomal rearrangement (ZAL2m) that predicts responses to social threat. Birds of the white-striped (WS) plumage morph (ZAL2m/ZAL2) respond to a territorial intrusion with high levels of vocal aggression, whereas birds of the tan-striped (TS) morph (ZAL2/ZAL2) respond with relatively little or no vocal aggression. The morphs also differ with respect to the formation of social attachments and parental provisioning rates; the phenotypes are thus characterized by a suite of correlated complex traits with a discrete genetic basis. The long-term goal of this research program is to fully exploit this unique model organism, which resembles humans with respect to many aspects of social behavior, to link gene expression and complex behavior in ways never before possible. Limited gene flow between the ZAL2 and ZAL2m haplotypes has led to the genetic differentiation of the rearranged chromosomal region, resulting in the accumulation of single nucleotide polymorphisms and other changes. The primary objective of this proposal is to assess the impact of these genetic forces on the genome and brain transcriptome, thus laying the groundwork to identify molecular mechanisms of behavioral dysregulation in future studies. We will combine the experience of two PIs: one with expertise in the behavioral neuroendocrinology of wild sparrows and the other in genome evolution. In Aim 1, we will identify and evaluate sequence differences between the two haplotypes, which will reveal a large number of potential functional polymorphisms that can then be explored experimentally. In Aim 2, we will use Next Generation techniques to sequence total mRNA from individuals for whom reactive aggression was quantified in a natural setting. We will then use weighted gene coexpression network analysis (WGCNA) of the mapped and quantified reads to identify modules of highly correlated genes associated with morph and reactive aggression. Together, the two aims will reveal candidate mechanisms underlying social strategies. This exploratory project will focus on responses to social threat, which are difficult to study in humans in a naturalistic setting. All behavioral manipulations and measurement will be conducted in the animals' natural habitat, making this project highly innovative. The project is significant because many mental disorders-including autism, depression, bipolar disorder and schizophrenia are characterized by dysregulated responses to social threat and because reactive aggression is often comorbid with risk-taking, substance abuse, and criminal behavior. Thus an understanding of the mechanisms underlying response to social threat is important for human health.
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0.907 |
2015 — 2019 |
Preuss, Todd M (co-PI) [⬀] Yi, Soojin |
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. |
Human Specific Brain Dna Methylation and Neuropsychiatric Diseases @ Georgia Institute of Technology
? DESCRIPTION (provided by applicant): Recent methodological advances in genomics and neuroscience have made it possible, for the first time, to determine how the human brain differs from that of other species. This research has revealed differences ranging from long-range neuronal connectivity to molecular changes, such as gene expression. Identifying these human-specific characteristics is vitally important for understanding common neurological and psychiatric diseases such as schizophrenia, autism, and Alzheimer's, diseases that have no definite counterparts in other primates and involve regions of the brain that underwent dramatic changes in size and internal organization in human evolution. However, the molecular mechanisms that underlie these diseases remain elusive. Our preliminary study of DNA methylation provides clues to these mechanisms, demonstrating that genes associated with neuropsychiatric disorders exhibit highly divergent DNA methylation patterns in human brains compared to non-human primate brains. Moreover, several human-specific gene co-expression networks that are strongly associated with neuropsychiatric disorders are enriched in genes that harbor human-specific DNA methylation signatures. In light of these observations, and of the emerging link between epigenomic markers and neuropsychiatric disorders, the systematic study of human epigenomic specializations promises to deepen our understanding of the molecular mechanisms that contribute to neuropsychiatric diseases and foster development of novel therapeutic interventions. The objectives of this project are to: (1) identify human-brain specific DNA methylation patterns; (2) elucidate the role of DNA methylation changes in the regulation of human-specific gene expression and co- expression networks; and (3) test the relevance of these epigenomic and transcriptomic changes in the context of neuropsychiatric diseases. We will examine two higher-order cortical regions from multiple human, chimpanzee, and macaque brains, drawing on the extensive collections of archival brain tissue available at the Yerkes National Primate Research Center. This comparative framework will enable us to pinpoint DNA methylation changes that accompanied changes in human brain structure and function. The link between human brain molecular specialization and human neuropsychiatric disorders will be verified by comparing control human brains to brains of schizophrenia patients, obtained from the Dallas Brain Collection (DBC) at UT Southwestern. The proposed studies of this multiple-PI and collaborator effort will leverage complementary and intersecting interests in epigenetics and evolution (Yi), comparative primate neurobiology (Preuss), and molecular neuroscience (Konopka). The application of our combined expertise to the analysis of the rich collection of DBC brain-disorder samples will promote discoveries of novel epigenetic mechanisms of neuropsychiatric disorders and provide the foundation for new insights and novel clinical approaches.
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1 |
2017 — 2020 |
Yi, Soojin Maney, Donna [⬀] Ortlund, Eric |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
A Model of Behavioral Evolution From Genotype to Phenotype
The evolution of behavior relies on changes at the level of the genome, yet few vertebrate behaviors can be traced directly to specific gene sequences. In this project, the research team will use a naturally-occurring animal model, the white-throated sparrow, to connect behavior with gene sequence in a concrete way. In this species, 50% of the birds have an unusual chromosome that makes them more aggressive. The chromosome is therefore an excellent tool for understanding how individual variation in gene expression contributes to variation in behavior. The team recently showed that animals with the unusual chromosome have higher expression of a type of steroid receptor in some areas of the brain. Here, the research group determines the genetic mechanisms, at the molecular level, that cause some birds to express more of these receptors than others. In so doing, the team demonstrates how responsiveness to steroid hormones is encoded in the genome. The work lends itself well to education and outreach because it illustrates basic biological concepts in a common backyard bird. Thus, it serves to integrate multiple units of a typical biology course in a way that is accessible to students. High school teachers are recruited to participate in the research and to develop lesson plans about genetics, hormones, brain anatomy, and social behavior. The PI also mentors high school students, undergraduates, and graduate students in the lab. More than 75% of the PI's mentees at Emory have been underrepresented minorities or women.
The evolution of behavior relies on changes at the level of the genome, yet few vertebrate behaviors can be traced directly to genetic sequences. In the white-throated sparrow (Zonotrichia albicollis), a chromosomal inversion segregates with an aggressive behavioral phenotype, offering a rare opportunity to connect genes and behavior in a concrete way. The inversion has captured the gene ESR1, which encodes estrogen receptor alpha (ERalpha). The research team recently showed that the local expression of ERalpha in the brain depends on the presence or absence of the inversion and that variation in ERalpha expression predicts the effect of genotype on territorial aggression. The research group uses in vitro reporter assays, bisulfite sequencing, and allele-specific quantitative PCR to identify the genetic and epigenetic mechanisms that contribute to variation in expression of ERalpha. The effects of selective ERalpha ligands on aggressive behavior in animals of each genotype is used to determine whether variation in ERalpha expression and function is causal for variation in territorial aggression. Because the team uses tissue from behaviorally characterized, free-living animals, the molecular and behavioral levels are integrated in the same animals to allow novel connections. The results provide an interdisciplinary, integrated model of how genetic change leads to phenotypic change. The work lends itself well to education and outreach because it illustrates basic biological concepts in a common backyard bird.
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0.907 |