Tracking shallow and dynamic chemoattractant gradients - how yeast cells amplify both internal and external signals to locate mating partners

跟踪浅层和动态趋化剂梯度——酵母细胞如何放大内部和外部信号来定位交配伙伴

基本信息

  • 批准号:
    2341919
  • 负责人:
  • 金额:
    $ 162.62万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
    Continuing Grant
  • 财政年份:
    2024
  • 资助国家:
    美国
  • 起止时间:
    2024-03-01 至 2028-02-29
  • 项目状态:
    未结题

项目摘要

This project will contribute to our understanding of gradient sensing, the ability of cells to sense small differences in chemical concentration across their surfaces, and thereby locate the source of the stimulus. This phenomenon is essential for the development and health of all organisms. The PI uses yeast cells as a model to study the molecular mechanisms underlying gradient sensing, which are thought to be broadly applicable to cells in more complex organisms. In previous studies, he discovered a “gradient tracking machine” that cells must assemble before they are able to sense the direction of the chemical source. In this investigation, he will continue to investigate how this machine functions to decode chemical gradients. During this project period, the PI and his senior research specialist will mentor select biology students from the City Colleges of Chicago, to enhance their chances of graduating from a four-year institution with a BS in a STEM field. The proposed undergraduate research and mentoring program is designed to inspire, instruct, advise, and support underrepresented students who are interested in a STEM career. Two outstanding candidates will be chosen to participate each year based on their academic potential and motivation to pursue a STEM major at a four-year institution. By participating in regular tutoring sessions, paid summer research internships in the PI’s lab, and public outreach events, students will gain experience conducting scientific research, an ability to critically evaluate the research of others, and practice presenting their work. This program is expected to increase the chances of eight students to succeed as science majors at four-year institutions. The investigation will also provide the PI's students with interdisciplinary training through interactions with collaborators who are experts in diverse areas.The best-known gradient-stimulated cellular outputs, chemotaxis (directed cell movement), and chemotropism (directed cell growth), are required for a wide range of biological processes. Although they ultimately exhibit quite different behavior, chemotactic and chemotropic cells face similar challenges: the responding cell must sense small differences in chemical concentration across its surface, determine the direction of the gradient source, and polarize its cytoskeleton toward it. The mating response of the budding yeast S. cerevisiae is chemotropic: mating cells interpret complex pheromone gradients and polarize their growth in the direction of the closest partner. Like many chemosensing cells, yeasts use G protein-coupled receptors to detect chemoattractant. The goal of this project is to understand how yeast cells accurately sense direction in shallow, complex, and dynamic pheromone gradients. Based on discoveries made in a previous project, the PI published a deterministic model of gradient sensing that explains, in broad terms, how yeast cells translate a vanishingly small differential of activated receptors across their surfaces into accurate and robust directional responses. Mating yeast initially ignore the pheromone gradient, as they first colocalize signaling, polarity, and trafficking proteins to the default polarity site they use for budding, building a “gradient tracking machine” (GTM). Once assembled, the GTM moves along the plasma membrane to the point of maximal pheromone concentration, where it marks the chemotropic site used for mating. The primary negative regulator of G-protein signaling, the RGS protein Sst2, is essential for this process, and phosphorylation of one of the G-protein subunits (Gbetagamma)plays a critical role. The priorities of this investigation are to learn how Sst2 is controlled in space and time, how the phosphorylation of the G protein subunit contributes to gradient tracking, and how dynamic intercommunication between GTMs enables mating partners to orient toward a common fusion site. These questions will be answered using imaging, genetic, biochemical, proteomic, and computational approaches.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.
这个项目将有助于我们理解梯度感应,即细胞感知其表面化学浓度的微小差异的能力,从而定位刺激的来源。这种现象对所有生物体的发展和健康都是必不可少的。PI使用酵母细胞作为模型来研究梯度感应的分子机制,这被认为广泛适用于更复杂的生物体中的细胞。在之前的研究中,他发现了一种“梯度跟踪机”,细胞必须先组装起来,才能感觉到化学源的方向。在这次调查中,他将继续研究这台机器如何解码化学梯度。在这个项目期间,PI和他的高级研究专家将指导从芝加哥城市学院挑选的生物学学生,以增加他们从四年制院校毕业并在STEM领域获得学士学位的机会。拟议的本科生研究和指导计划旨在激励、指导、建议和支持对STEM职业感兴趣的代表不足的学生。根据他们的学术潜力和在四年制院校攻读STEM专业的动机,每年将选出两名优秀的候选人参加。通过参加定期辅导课程、在PI实验室的带薪暑期研究实习和公共宣传活动,学生们将获得开展科学研究的经验,具有批判性评估他人研究的能力,并练习展示他们的工作。这一计划预计将增加8名学生在四年制院校成功攻读理科专业的机会。这项研究还将通过与不同领域的专家合作者的互动,为PI的学生提供跨学科培训。最著名的梯度刺激细胞输出、趋化(定向细胞移动)和趋化(定向细胞生长)是广泛的生物过程所必需的。尽管趋化细胞和趋化细胞最终表现出完全不同的行为,但它们面临着相似的挑战:响应的细胞必须感觉到其表面化学浓度的微小差异,确定梯度源的方向,并将其细胞骨架极化向它。萌芽酵母的交配反应是趋化性的:交配细胞解释复杂的信息素梯度,并将它们的生长极化在最接近的伴侣的方向上。像许多化学传感细胞一样,酵母菌使用G蛋白偶联受体来检测化学诱导剂。这个项目的目标是了解酵母细胞如何在浅的、复杂的和动态的信息素梯度中准确地感知方向。基于前一个项目中的发现,PI发布了一个确定的梯度感应模型,该模型广义地解释了酵母细胞如何将其表面上激活的受体的微小差异转化为准确而强大的定向反应。交配酵母最初忽略信息素梯度,因为它们首先将信号、极性和运输蛋白质共同定位到它们用于发芽的默认极性位置,从而建立一个“梯度跟踪机”(GTM)。一旦组装,GTM就会沿着质膜移动到信息素浓度最高的地方,在那里它标志着用于交配的趋化部位。G蛋白信号的主要负调控因子RGS蛋白Sst2在这一过程中是必不可少的,而G蛋白的一个亚基(Gbetagamma)的磷酸化起着关键作用。这项研究的重点是了解Sst2是如何在空间和时间上受到控制的,G蛋白亚单位的磷酸化如何有助于梯度跟踪,以及GTM之间的动态相互通信如何使交配伙伴能够定位到共同的融合位点。这些问题将使用成像、遗传、生化、蛋白质和计算方法来回答。这一奖项反映了NSF的法定使命,并通过使用基金会的智力优势和更广泛的影响审查标准进行评估,被认为值得支持。

项目成果

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David Stone其他文献

Genome-wide association analysis of Dementia with Lewy bodies reveals unique genetic architecture
痴呆与路易体的全基因组关联分析揭示了独特的遗传结构
  • DOI:
  • 发表时间:
    2017
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Rita Guerreiro;Owen A. Ross;Célia Kun;Dena G. Hernandez;Tatiana Orme;John D. Eicher;Claire Shepherd;L. Parkkinen;Lee Darwent;Michael G. Heckman;Sonja;W. Scholz;Juan C. Troncoso;O. Pletnikova;Olaf Ansorge;J. Clarimón;Alberto;Lleó;E. Morenas;Lorraine Clark;Lawrence Honig;Karen Marder;A. Lemstra;E. Rogaeva;P. S. George;E. Londos;Henrik;Zetterberg;I. Barber;A. Braae;K. Brown;Kevin Morgan;Claire;Troakes;S. Al;T. Lashley;J. Holton;Y. Compta;Vivianna;Van Deerlin;G. Serrano;Thomas G. Beach;S. Lesage;D. Galasko;E. Masliah;Isabel Santana;P. Pástor;M. Diez;M. Aguilar;Pentti;J. Tienari;L. Myllykangas;M. Oinas;T. Revesz;Andrew J. Lees;F. Brad;Boevé;R. C. Petersen;T. Ferman;V. Escott;;Radford;Nigel J. Cairns;John C. Morris;S. Pickering;David Mann;M. Glenda;Halliday;John Hardy;J. Trojanowski;Dennis W. Dickson;Andy Singleton;David Stone;J. Bras
  • 通讯作者:
    J. Bras
Calcite Biomineralisation in the Caves of Nullarbor Plains, Australia
澳大利亚纳拉伯平原洞穴中的方解石生物矿化
  • DOI:
  • 发表时间:
    2005
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Annalisa K. Contos;J. James;A. Holmes;B. Heywood;M. Gillings;P. Rogers;David Stone
  • 通讯作者:
    David Stone
METABOLISM OF PHENYLALANINE AND TYROSINE BY ESCHERICHIA COLI STRAIN K-12
  • DOI:
    10.1016/s0021-9258(18)65596-6
  • 发表时间:
    1954-06-01
  • 期刊:
  • 影响因子:
  • 作者:
    Sofia Simmonds;Marian T. Dowling;David Stone
  • 通讯作者:
    David Stone
UTILIZATION OF PROLINE PEPTIDES BY A PROLINELESS MUTANT OF ESCHERICHIA COLI
  • DOI:
    10.1016/s0021-9258(19)57121-6
  • 发表时间:
    1953-05-01
  • 期刊:
  • 影响因子:
  • 作者:
    David Stone;Henry D. Hoberman
  • 通讯作者:
    Henry D. Hoberman
Factors Associated with Preference of Choice of Aortic Aneurysm Repair in the PReference for Open Versus Endovascular repair of AAA (PROVE-AAA) study.
与 AAA 开放与血管内修复 (PROVE-AAA) 研究 PReference 中主动脉瘤修复选择偏好相关的因素。
  • DOI:
    10.1016/j.jvs.2022.06.018
  • 发表时间:
    2022
  • 期刊:
  • 影响因子:
    4.3
  • 作者:
    M. Eid;J. Barnes;Kunal Mehta;Zachary J. Wanken;J. Columbo;Ravinder Kang;K. Newhall;V. Halpern;J. Raffetto;P. Kougias;Peter Henke;G. Tang;L. Mureebe;J. Johanning;Edith Tzeng;Salvatore T. Scali;David Stone;B. Suckow;Eugeen Lee;Shipra Arya;Kristine C. Orion;Jessica O’Connell;Benjamin Brooke;Daniel Ihnat;H. Dosluoglu;Wei Zhou;Peter Nelson;Emily Spangler;Michael Barry;Brenda Sirovich;P. Goodney
  • 通讯作者:
    P. Goodney

David Stone的其他文献

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{{ truncateString('David Stone', 18)}}的其他基金

RCN: Finding Your Inner Modeler - an interdisciplinary community solving problems in systems biology
RCN:寻找你的内在建模者 - 一个解决系统生物学问题的跨学科社区
  • 批准号:
    2003415
  • 财政年份:
    2020
  • 资助金额:
    $ 162.62万
  • 项目类别:
    Continuing Grant
How yeast sense direction in shallow pheromone gradients
酵母如何感知浅信息素梯度中的方向
  • 批准号:
    1818067
  • 财政年份:
    2018
  • 资助金额:
    $ 162.62万
  • 项目类别:
    Standard Grant
TransEnergy - Road to Rail Energy Exchange (R2REE)
TransEnergy - 路铁能源交换 (R2REE)
  • 批准号:
    EP/N022289/1
  • 财政年份:
    2016
  • 资助金额:
    $ 162.62万
  • 项目类别:
    Research Grant
Workshops: Finding your inner modeler: how computational biology can advance your research and how to get started; June/July, 2017-2019; Chicago, Illinois
研讨会:寻找你的内在建模者:计算生物学如何推进你的研究以及如何开始;
  • 批准号:
    1649160
  • 财政年份:
    2016
  • 资助金额:
    $ 162.62万
  • 项目类别:
    Standard Grant
Empirical and mathematical approaches to study gradient sensing using yeast as a model
使用酵母作为模型研究梯度传感的经验和数学方法
  • 批准号:
    1415589
  • 财政年份:
    2014
  • 资助金额:
    $ 162.62万
  • 项目类别:
    Standard Grant
Ultra Battery Feasibility - Investigation into the combined battery-supercapacitor for hybrid electric vehicle (HEV) applications
超级电池可行性 - 针对混合动力电动汽车 (HEV) 应用的组合电池-超级电容器的研究
  • 批准号:
    EP/H050221/1
  • 财政年份:
    2010
  • 资助金额:
    $ 162.62万
  • 项目类别:
    Research Grant
Heterotrimeric G Protein Regulation of Chemotropism in Yeast
异源三聚体 G 蛋白对酵母趋化性的调节
  • 批准号:
    1024718
  • 财政年份:
    2010
  • 资助金额:
    $ 162.62万
  • 项目类别:
    Standard Grant
Advanced Cell State of Function Models for HEV operation
适用于 HEV 运行的高级细胞功能状态模型
  • 批准号:
    EP/D079527/1
  • 财政年份:
    2006
  • 资助金额:
    $ 162.62万
  • 项目类别:
    Research Grant
G Protein Regulation of a Microtubule Motor Protein in Yeast
酵母中微管运动蛋白的 G 蛋白调节
  • 批准号:
    0453964
  • 财政年份:
    2005
  • 资助金额:
    $ 162.62万
  • 项目类别:
    Continuing Grant
Heterotrimeric G Protein-Mediated Cellular Polarization in Yeast
异源三聚体 G 蛋白介导的酵母细胞极化
  • 批准号:
    0218081
  • 财政年份:
    2002
  • 资助金额:
    $ 162.62万
  • 项目类别:
    Standard Grant

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Evaluation of globally dynamic trends for potential utilization of shallow geothermal energy under climate change, and its application and standardization
气候变化背景下全球浅层地热能潜在利用动态趋势评价及其应用和标准化
  • 批准号:
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Ecological study toward the vegetation management based on the dynamic regime theory for shallow lake ecosystem
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