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CAREER: Initiation of Cell Size Patterning in Arabidopsis

职业生涯：拟南芥细胞大小模式的启动

基本信息

批准号：
1553030
负责人：
Adrienne Roeder
金额：
$ 98.85万
依托单位：
Cornell University
依托单位国家：
美国
项目类别：
Continuing Grant
财政年份：
2016
资助国家：
美国
起止时间：
2016-03-01 至 2024-02-29
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1553030&HistoricalAwards=false
关键词：
CAREER Initiation Cell Size Patterning

项目摘要

With a rapidly growing population and decreasing farmland, the world will need to dramatically increase crop yields. The cells in the edible parts of corn, beans, rice, wheat, and peas undergo a specialized process called endoreduplication where the cells replicate their DNA many times. Although individual cells undergo different amounts of endoreduplication, the proportion of cells remains constant from plant to plant. When geneticists try to increase endoreduplication, they find that the response of seemingly identical cells is somewhat random: some cells respond strongly, some moderately, and some not at all. This observation raises one of the biggest questions in developmental biology: how do identical cells make different decisions? The proposed research will investigate the counterintuitive hypothesis that individual plant cells make these decisions about how much to endoreduplicate utilizing small, random molecular differences. This hypothesis is surprising: biologists would normally expect randomness to be suppressed, since development is highly reproducible, always creating the same proportion of endoreduplicated cells. Instead, randomness may in fact be required to produce this regular portion of endoreduplicated cells. Testing this hypothesis will require advanced use of computers to examine individual cells over time. University students and middle school girls will simultaneously be involved in this analysis as well as being trained in computational skills.Endoreduplicating cells of crop plants are buried deep within the seed coat where they are experimentally inaccessible. Endoreduplication will thus be studied in Arabidopsis thaliana sepals, whose epidermal cells are accessible for live imaging as they endoreduplicate. The transcription factor Arabidopsis thaliana MERISTEM LAYER1 (ATML1) drives sepal endoreduplication, and may cause it to occur randomly. Since ATML1 is expressed in all epidermal cells, it is unclear how ATML1 causes only a few cells to endoreduplicate. Preliminary data show that ATML1 triggers endoreduplication in a dosage-dependent manner: high ATML1 makes all epidermal cells endoreduplicate, low ATML1 prevents any endoreduplication, and individual sepal cells have varying levels of ATML1. The hypothesis tested here is that randomly fluctuating ATML1 causes different levels of endoreduplication in different cells; a few cells exceed ATML1's threshold, triggering endoreduplication, while other cells remain below the threshold and do not endoreduplicate. In Aim 1, we will determine whether ATML1 fluctuations initiate endoreduplication. The associated education goal will be to work with undergraduate students to analyze images generated in this aim. For Aim 2, we will determine whether ATML1 feedback loops drive endoreduplication by amplifying differences in ATML1 expression and, in an associated educational aim, students will write and publish a computational modeling glossary to better understand the newly generated models. Finally, in Aim 3 we will determine the molecular mechanism through which ATML1 induces endoreduplication in a dosage-dependent manner. We will also develop an outreach to middle school students for the analysis of images from Aim 3 in a hands-on, web-based image analysis workshop.

随着人口的快速增长和耕地的减少，世界将需要大幅提高农作物产量。玉米、豆类、大米、小麦和豌豆的可食用部分的细胞经历一个称为核内复制的特殊过程，细胞多次复制其DNA。虽然单个细胞经历不同数量的核内复制，但细胞的比例在植物与植物之间保持恒定。当遗传学家试图增加核内复制时，他们发现看似相同的细胞的反应有些随机：有些细胞反应强烈，有些细胞反应温和，有些根本没有。这一观察结果提出了发育生物学中最大的问题之一：相同的细胞如何做出不同的决定？这项研究将调查一个违反直觉的假设，即单个植物细胞利用微小的随机分子差异来决定核内复制多少。这个假设令人惊讶：生物学家通常会期望随机性被抑制，因为发育是高度可重复的，总是产生相同比例的核内复制细胞。相反，随机性实际上可能需要产生核内复制细胞的这种规则部分。检验这一假设需要先进的计算机技术来检测单个细胞。大学生和中学女生将同时参与这项分析，并接受计算技能培训。作物植物的内复制细胞深埋在种皮中，实验无法接近。因此，内复制将在拟南芥萼片，其表皮细胞是可访问的活成像，因为他们内复制研究。转录因子拟南芥MERISTEM LAYER 1（ATML 1）驱动萼片核内复制，并可能导致其随机发生。由于ATML 1在所有表皮细胞中表达，因此尚不清楚ATML 1如何仅引起少数细胞核内复制。初步数据显示，ATML 1以剂量依赖性方式触发核内复制：高ATML 1使所有表皮细胞核内复制，低ATML 1阻止任何核内复制，并且单个萼片细胞具有不同水平的ATML 1。这里测试的假设是，随机波动的ATML 1导致不同细胞中不同水平的核内复制;少数细胞超过ATML 1的阈值，触发核内复制，而其他细胞保持低于阈值，不进行核内复制。在目标1中，我们将确定ATML 1波动是否启动核内复制。相关的教育目标将是与本科生一起分析在此目标中生成的图像。对于目标2，我们将确定ATML 1反馈环是否通过放大ATML 1表达的差异来驱动核内复制，并且在相关的教育目标中，学生将编写并发布计算建模词汇表，以更好地理解新生成的模型。最后，在目标3中，我们将确定ATML 1以剂量依赖性方式诱导核内复制的分子机制。我们还将在一个基于网络的动手图像分析研讨会上向中学生推广目标3中的图像分析。