NSF Postdoctoral Fellowship in Biology: Rewriting the Code: Elucidating how early life adversity alters DNA to affect amygdala-related behavior

NSF 生物学博士后奖学金：重写代码：阐明早年逆境如何改变 DNA 从而影响杏仁核相关行为

• 批准号: 2208822
• 负责人: Amelia Cuarenta
• 金额: $ 13.8万
• 依托单位: Cuarenta, Amelia
• 依托单位国家: 美国
• 项目类别: Fellowship Award
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-02-01 至 2025-01-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2208822&HistoricalAwards=false
• 关键词: NSF; Postdoctoral; Fellowship; Biology; Rewriting

This action funds an NSF Postdoctoral Research Fellowship in Biology for FY 2022, Broadening Participation of Groups Underrepresented in Biology. The Fellowship supports a research and training plan for the Fellow that will increase the participation of groups underrepresented in biology. Events experienced early in life can have lasting consequences for brain development and behavior. Recent research suggests that mobile genetic elements (retrotransposons), which are so named because they can move around in the genome, could be a mechanism by which early life events cause lasting effects. This research will investigate how changes in the early life environment alter mobility of a retrotransposon, called long interspersed element 1 (L1), in the brain and whether these changes affect later social behavior in rats. This research will enhance understanding of how the environment can impact behavior. The project will also broaden participation for underrepresented groups in biology through training of the fellow, workshops hosted through a collaboration with local organizations committed to diversity and inclusion, mentorship of students, and development of outreach networks for underrepresented scientists in the Philadelphia area.This research will investigate how different environmental conditions (exposure to aversive odors) alter L1 insertion sites in the amygdala and whether these changes affect amygdala-related behavior in rats. For the first aim, the fellow will use molecular genetic approaches to determine number and location of de novo L1 in amygdala cells and determine if a given endpoint is altered by early life experiences. This research will be the first to use REBELseq in rats to identify the location and number of de novo L1 insertions. These results will help resolve an ongoing debate in the field about whether de novo L1 insertions are randomly inserted or inserted systematically. For the second aim, the fellow will assess the functional consequence of L1 knockdown in the amygdala. Prior research found a negative correlation between L1 insertions and juvenile social play. Utilizing antisense oligonucleotides, the fellow will transiently knockdown L1 mRNA within the amygdala during the neonatal period and assess whether there is a resultant increase in social play behavior or anxiety-related behavior during the juvenile stage of development. This research will enhance understanding of how the environment can impact behavior and document de novo L1 insertions and their relevance during development. The fellow will partner with two different diversity and inclusion programs to support underrepresented minority students by creating workshops, serving as a panel member, and directly mentoring students. Additionally, the fellow will create a networking event for postdoctoral researchers to increase community engagement and collaboration at the Philadelphia chapter of Society for Neuroscience meeting.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.

这项行动资助了2022财年的NSF生物学博士后研究奖学金，扩大了生物学中代表性不足的群体的参与。该研究金支持研究员的一项研究和培训计划，该计划将增加在生物学领域代表性不足的群体的参与。生命早期经历的事件可能对大脑发育和行为产生持久的影响。最近的研究表明，移动的遗传元件（反转录转座子）（之所以这样命名是因为它们可以在基因组中移动）可能是早期生命事件造成持久影响的一种机制。这项研究将研究早期生活环境的变化如何改变逆转录转座子（称为长散布元件1（L1））在大脑中的移动性，以及这些变化是否会影响大鼠后来的社会行为。这项研究将加深对环境如何影响行为的理解。该项目还将通过培训研究员、与致力于多样性和包容性的当地组织合作举办讲习班、指导学生，并为费城地区代表性不足的科学家建立外展网络。这项研究将调查不同的环境条件如何影响（暴露于令人厌恶的气味）改变杏仁核中的L1插入位点，以及这些变化是否影响大鼠杏仁核相关行为。对于第一个目标，该研究员将使用分子遗传学方法来确定杏仁核细胞中从头L1的数量和位置，并确定给定的终点是否被早期生活经历改变。这项研究将是第一个在大鼠中使用REBELseq来确定从头L1插入的位置和数量。这些结果将有助于解决该领域正在进行的争论，即从头L1插入是随机插入还是系统插入。对于第二个目标，研究员将评估杏仁核中L1敲低的功能后果。先前的研究发现，L1插入和青少年的社会游戏之间存在负相关。利用反义寡核苷酸，该研究员将在新生儿时期瞬时敲低杏仁核内的L1 mRNA，并评估在发育的青少年阶段是否会导致社交游戏行为或焦虑相关行为的增加。这项研究将加深对环境如何影响行为的理解，并记录从头L1插入及其在发育过程中的相关性。该研究员将与两个不同的多样性和包容性计划合作，通过创建研讨会，担任小组成员和直接指导学生来支持代表性不足的少数民族学生。此外，该研究员将为博士后研究人员创建一个网络活动，以增加神经科学学会费城分会会议上的社区参与和合作。该奖项反映了NSF的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。