Using Directed Evolution to Srudy the Origins of Multicellular Development

利用定向进化研究多细胞发育的起源

• 批准号: 10807198
• 负责人: William Croft Ratcliff
• 金额: $ 1.54万
• 依托单位: GEORGIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10807198
• 关键词: Agar; Apoptosis; Biogenesis; Biomedical Research; Cell Wall; Cells; Cellularity; Communication; Data; Directed Molecular Evolution; Doctor of Philosophy; Evolution; Funding; Gene Expression; Generations; Genes; Grant; Growth; Head Start Program; Immobilization; Internships; Location; Machine Learning; Maps; Measures; Mentors; Methods; Paper; Postdoctoral Fellow; Procedures; Process; Research; Ribosomes; Time; Work; Yeast Model System; Yeasts; biological adaptation to stress; cell type; cellular development; doctoral student; imaging Segmentation; improved; meetings; phenotypic data; programs; protein expression; single-cell RNA sequencing; skills; undergraduate student

Grant R35GM138030 utilizes directed evolution to study the evolution of multicellularity in the 'snowflake yeast' model system. The proposed work involved using single cell RNA-seq to examine the origin of multiple cell types over ~5,000 generations of evolution. Snowflake yseat evolve three distinct cell states, with elevated gene expression related to ribosomal processes, cell wall biogenesis, and stress response and programmed cell death, respectively. During a recent internship, undergraduate Luis Felipe Cedeno Perez developed a method to measure real-time single-cell phenotypic data in developing snowflake yeast clusters via soft-agar immobilization and image segmentation. He used machine learning to construct cell fate maps. His internship will end in April, 2023. If funded, Luis Felipe's summer project will allow him to complete his project, by integrating differential gene/protein expression into his segmentation pipeline, allowing for the construction of cell fate lineage maps and examination of location-dependent gene expression during ontogeny. Luis Felipe will gain expertise in experimental procedures and computational approaches, working closely with a postdoc in the lab for in-lab mentoring as well as meeting regularly with the PI. He will also participate in activities to improve his project management, scientific communication, and teamwork skills. The supplement will enable Luis Felipe to finish his project and generate the data required for a first-author paper, making him competitive for top-tier PhD programs in biomedical research. If he joins the Ratcliff lab as a PhD student, the project will give him a head start on his PhD thesis research and make him more competitive for proposals that would fund his PhD research.

Grant R35 GM 138030利用定向进化研究“雪花”中多细胞的进化 酵母模型系统。拟议的工作涉及使用单细胞RNA-seq来检查多个基因的起源。 细胞类型超过5,000代的进化。雪花yseat进化出三种不同的细胞状态， 与核糖体过程、细胞壁生物发生、应激反应和程序化细胞相关的基因表达 死亡，分别。在最近的一次实习中，本科生Luis Felipe Cedeno Perez开发了一种方法， 通过软琼脂测量雪花酵母团的实时单细胞表型数据 固定和图像分割。他使用机器学习来构建细胞命运图。实习 将于2023年4月结束。如果得到资助，路易斯·费利佩的夏季项目将使他能够完成他的项目， 将差异基因/蛋白质表达整合到他的分割管道中，允许构建 细胞命运谱系图和个体发育过程中位置依赖性基因表达的检查。 Luis Felipe将获得实验程序和计算方法方面的专业知识，与 实验室的博士后进行实验室内指导，并定期与PI会面。他还将参加 活动，以提高他的项目管理，科学沟通和团队合作技能。补充剂 将使路易斯·费利佩能够完成他的项目，并生成第一作者论文所需的数据，使他成为第一作者。 在生物医学研究方面的顶级博士课程竞争。如果他作为博士生加入拉特克利夫实验室， 这个项目将使他在博士论文研究方面领先一步，并使他在那些 会资助他的博士研究

项目成果

Multicellularity drives ecological diversity in a long-term evolution experiment.

在长期进化实验中，多细胞性驱动了生态多样性。

• DOI: 10.1038/s41559-024-02391-y
• 发表时间: 2024
• 期刊: Nature ecology & evolution
• 影响因子: 16.8

A non-adaptive explanation for macroevolutionary patterns in the evolution of complex multicellularity.

对复杂多细胞进化中宏观进化模式的非适应性解释。

• DOI: 10.1101/2023.11.11.566713
• 发表时间: 2023
• 期刊: bioRxiv : the preprint server for biology
• 作者: Bingham,EmmaP;Ratcliff,WilliamC
• 通讯作者: Ratcliff,WilliamC

A nonadaptive explanation for macroevolutionary patterns in the evolution of complex multicellularity.

对复杂多细胞进化中宏观进化模式的非适应性解释。

• DOI: 10.1073/pnas.2319840121
• 发表时间: 2024
• 期刊: Proceedings of the National Academy of Sciences of the United States of America
• 影响因子: 11.1
• 作者: Bingham,EmmaP;Ratcliff,WilliamC
• 通讯作者: Ratcliff,WilliamC

The science of storytelling: the David Attenborough style of scientific presentation

讲故事的科学：大卫·阿滕伯勒的科学呈现风格

• DOI: 10.1016/j.molmed.2023.05.002
• 发表时间: 2023
• 期刊: Trends in Molecular Medicine
• 影响因子: 13.6
• 作者: Ratcliff, William C.

Cellular organization in lab-evolved and extant multicellular species obeys a maximum entropy law.

• DOI: 10.7554/elife.72707
• 发表时间: 2022-02-21
• 期刊: eLife
• 影响因子: 7.7
• 作者: Day TC;Höhn SS;Zamani-Dahaj SA;Yanni D;Burnetti A;Pentz J;Honerkamp-Smith AR;Wioland H;Sleath HR;Ratcliff WC;Goldstein RE;Yunker PJ
• 通讯作者: Yunker PJ