The Genetics and Neurobiology of Parental Care in Wild Mice

野生小鼠父母照顾的遗传学和神经生物学

• 批准号: 9540965
• 负责人: Andrés Bendesky
• 金额: $ 24.9万
• 依托单位: COLUMBIA UNIV NEW YORK MORNINGSIDE
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2020-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9540965
• 关键词: Achievement; Adult; Advisory Committees; Affect; Amino Acid Sequence; Animals; Area; Behavior; Behavioral; Behavioral Genetics; Biological; Biology; Brain; Brain region; CRISPR/Cas technology; Candidate Disease Gene; Caring; Child; Child Development; Child health care; Childhood; Chromosome Mapping; Cognitive; Decision Making; Development; Development Plans; Doctor of Philosophy; Drug Targeting; Elements; Environment; Equipment; FOS gene; Fathers; Feedback; Gene Expression Profiling; Gene Targeting; Genes; Genetic; Genetic Screening; Genetic Variation; Genome; Genotype; Goals; Growth; Human; Human Development; Individual; Infant Care; Institutes; Knowledge; Label; Laboratories; Laboratory mice; Lead; Learning; Mammals; Maps; Measures; Mentors; Messenger RNA; Microtus; Molecular; Molecular Analysis; Molecular Profiling; Mothers; Motivation; Mouse Strains; Mus; Nervous System Physiology; Neurobiology; Neurons; Neurosciences; Parents; Partner in relationship; Pathway interactions; Peromyscus; Pharmacology; Phase; Postpartum Depression; Prevention; Psychologist; Psychotic Disorders; Quantitative Genetics; Quantitative Trait Loci; Research; Resources; Sister; Social Behavior; Source; Structure; Targeted Research; Techniques; Technology; Testing; Tissues; Training; Transgenic Organisms; Universities; Variant; career; career development; differential expression; disorder risk; forward genetics; gene product; genetic analysis; genetic approach; genetic element; genetic variant; human disease; interest; mind control; molecular marker; neglect; neural circuit; neuronal circuitry; neuronal patterning; next generation sequencing; offspring; programs; psychologic; public health relevance; pup; social; transcriptome; transcriptome sequencing

 DESCRIPTION (provided by applicant): Parental care is critical to child survival and healthy human development, yet we know little about how the brain controls parental care and about biological sources of variation in this behavior. The proposed research uses two species of Peromyscus mice that differ greatly in their parental care to identify genes and neuronal mechanisms that regulate parental care in mammals. To identify genetic variants, the candidate will perform a genetic analysis using a large cross between the two species. To define brain regions involved in parental care, the candidate will compare brain-wide patterns of neuronal activity between mice caring for their pups and mice ignoring them. He will then analyze the genes expressed in the identified brain regions to find genes that differ between the species. Identified genes that are common to both the genetic analysis and the gene expression analysis will point to specific molecular pathways relevant to parental care. These pathways will be further tested with pharmacology and transgenics techniques. Candidate and his career goals. The candidate, Dr. Andrés Bendesky, has a strong background in quantitative genetics and neuroscience, having spent his PhD identifying genetic variants that modulate decision-making and characterizing how these variants modify neuronal circuits. Dr. Bendesky's long-term career goal is to develop an independent research program devoted to understanding the causes and mechanisms of variation in behavior between individuals. He is particularly interested in understanding how genetic variation modifies the brain to alter behavior. The goals of this proposal are to define the genetic elements responsible for differences in parental care between two closely related species of wild mice and to characterize the neurobiological pathways involved in such variation in behavior. Key elements of the research career development plan. The research proposed for the mentored phase of the proposal will be conducted in the laboratories of Dr. Hopi Hoekstra and Dr. Catherine Dulac at Harvard University. Dr. Hoekstra is an expert in Peromyscus biology, behavior and genetics. Dr. Dulac is an expert in the neurobiology of social behaviors, including parental behavior. Their expertise optimally synergizes to guide the research proposed here. The candidate has an Advisory Committee composed of Dr. Elizabeth Spelke (Harvard), a distinguished cognitive developmental psychologist, and Dr. Rudolf Jaenisch (MIT, Whitehead Institute), an expert in animal genome manipulation. Both mentors and advisors will guide the candidate in his research and in the transition to an independent research career. The environment at Harvard and in the Hoekstra/Dulac laboratories is spectacular, providing excellent facilities and all the needed equipment for the proposed research. It is an ideal training place: remarkable seminars, opportunities to present research progress and receive feedback, and resources to help transition to independence.

 描述（由申请人提供）：父母照顾对儿童生存和人类健康发展至关重要，但我们对大脑如何控制父母照顾以及这种行为的生物学来源知之甚少。这项拟议的研究使用了两种在父母照顾方面差异很大的Peromyscus小鼠，以确定调节哺乳动物父母照顾的基因和神经元机制。为了识别遗传变异，候选人将使用两个物种之间的大型杂交进行遗传分析。为了确定参与父母照顾的大脑区域，候选人将比较照顾幼崽的小鼠和忽视它们的小鼠之间的全脑神经元活动模式。然后，他将分析在已识别的大脑区域中表达的基因，以找到物种之间的差异基因。遗传分析和基因表达分析所共有的已鉴定基因将指向与亲本护理相关的特定分子途径。这些途径将进一步测试与药理学和转基因技术。候选人及其职业目标。候选人Andrés Bendesky博士在数量遗传学和神经科学方面有很强的背景，他在博士学位期间鉴定了调节决策的遗传变异，并描述了这些变异如何改变神经元回路。Bendesky博士的长期职业目标是开发一个独立的研究项目，致力于了解个体之间行为变化的原因和机制。他特别感兴趣的是了解遗传变异如何改变大脑以改变行为。这项建议的目标是确定负责两个密切相关的野生小鼠物种之间的父母照顾的差异的遗传因素，并表征参与这种行为变化的神经生物学途径。研究职业发展计划的关键要素。建议的指导阶段的研究将在哈佛大学的Hopi Hoekstra博士和Catherine迪拉克博士的实验室进行。Hoekstra博士是Peromyscus生物学、行为学和遗传学方面的专家。迪拉克博士是社会行为神经生物学方面的专家，包括父母行为。他们的专业知识最佳地协同作用，以指导这里提出的研究。候选人有一个咨询委员会，由著名的认知发展心理学家伊丽莎白·斯佩尔克博士（哈佛）和动物基因组操纵专家鲁道夫·耶尼施博士（麻省理工学院怀特黑德研究所）组成。导师和顾问将指导候选人进行研究，并过渡到独立的研究生涯。在哈佛和Hoekstra/迪拉克实验室的环境是壮观的，提供优良的设施和所有所需的设备，为拟议的研究。这是一个理想的培训场所：出色的研讨会，展示研究进展和接收反馈的机会，以及帮助过渡到独立的资源。