International Research Fellowship Program: Systems Biology of Glucose Repression in Yeast for Metabolic Engineering
国际研究奖学金计划:代谢工程酵母中葡萄糖抑制的系统生物学
基本信息
- 批准号:0504168
- 负责人:
- 金额:--
- 依托单位:
- 依托单位国家:美国
- 项目类别:Fellowship Award
- 财政年份:2005
- 资助国家:美国
- 起止时间:2005-06-01 至 2007-12-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
0504168JewettThe International Research Fellowship Program enables U.S. scientists and engineers to conduct three to twenty-four months of research abroad. The program's awards provide opportunities for joint research, and the use of unique or complementary facilities, expertise and experimental conditions abroad.This award will support a twenty-two month research fellowship by Dr. Michael C. Jewett to work with Dr. Jens Nielsen at Technical University of Denmark's Center for Microbial Biotechnology (CMB) in Lyngby, Denmark.Genetically engineering cells for production of valuable protein therapeutics and secondary metabolites is widely exploited in the pharmaceutical and chemical industries. However, achieving desired phenotypes that are, in general, not the "Darwinian optimum," presents a formidable challenge given the complex nature of the catalytic inventory, metabolic pathways, signaling circuits, and regulatory networks of microorganisms. To rationally design cell factories, we must use system-level methods to gain an understanding of the physiological information necessary to rewire cellular control element. The objective of this project is to identify key components of glucose repression in Saccharomyces cerevisiae using systems biology for design of glucose de-repressed strains. Such strains are industrially attractive for improving baker's yeast production from molasses, bioethanol production from sugar mixtures, and heterologous protein production. To achieve this goal, the PI and host will combine genome-scale metabolic models with DNA array and metabolite profiling data of several glucose repression mutants. Detailed characterization of these mutants by model guided analysis of global cellular function will allow mapping of all pleotrophic effects, identification of co-regulated metabolic patterns, and subsequent engineering of desired strains. In addition to accomplishing this main objective, ther study has several expected deliverables. First, novel algorithms for integration of data from both the transcriptome and the metabolome will be developed. Second, new analytical methods for metabolite profiling based on direct infusion mass spectrometry will be designed. Third, the role of regulatory elements involved in glucose sensing and repression will be clarified.This study will have a broad impact on the field of systems biology and yeast genetics/physiology. Particularly, the novel algorithms will find wide use in metabolic engineering and directly enhance our capability to design "made to order" organisms. In addition, the development of glucose de-repressed strains of S. cerevisiae will increase their utility as industrial production hosts. Furthermore, since glucose repression in yeast serves as a model for nutrient sensing in eukaryotic cells, the development of efficient algorithms for this system may be applied to mapping of signal transduction pathways in higher eukaryotes - including humans. Progress in this research area will directly enhance and complement many technologies in the scientific community while generating a valuable international partnership. The CMB has a strong international position in metabolic engineering, fermentation, physiology, functional genomics, and systems biology of eukaryotic microorganisms.
0504168 Jewett国际研究奖学金计划使美国科学家和工程师能够在国外进行三到二十四个月的研究。 该计划的奖项提供了联合研究的机会,以及使用独特或互补的设施,专业知识和国外的实验条件。朱厄特将与丹麦林比的丹麦技术大学微生物技术中心(CMB)的延斯·尼尔森博士合作。然而,实现所需的表型,一般来说,不是“达尔文最优”,提出了一个艰巨的挑战,考虑到复杂的性质的催化库存,代谢途径,信号传导电路,和调控网络的微生物。为了合理地设计细胞工厂,我们必须使用系统级的方法来了解重新连接细胞控制元件所需的生理信息。 该项目的目标是利用系统生物学来设计葡萄糖去抑制菌株,以确定酿酒酵母中葡萄糖抑制的关键成分。这样的菌株在工业上对于改善来自糖蜜的面包酵母生产、来自糖混合物的生物乙醇生产和异源蛋白质生产是有吸引力的。 为了实现这一目标,PI和宿主将联合收割机将基因组规模的代谢模型与几种葡萄糖阻遏突变体的DNA阵列和代谢物谱数据相结合。通过模型引导的全局细胞功能分析对这些突变体的详细表征将允许绘制所有多营养效应,鉴定共调节的代谢模式,以及随后的所需菌株的工程化。除了完成这一主要目标外,该研究还有几个预期的可交付成果。首先,将开发用于整合来自转录组和代谢组的数据的新算法。其次,将设计基于直接注入质谱法的代谢物谱分析新方法。第三,阐明了葡萄糖传感和阻遏过程中调控元件的作用,对系统生物学和酵母遗传学/生理学领域产生了广泛的影响。特别是,新的算法将在代谢工程中得到广泛的应用,并直接提高我们设计“定制”生物体的能力。此外,葡萄糖去阻遏菌株的开发也是一个重要的研究方向。酿酒酵母将增加它们作为工业生产宿主的效用。此外,由于酵母中的葡萄糖阻遏充当真核细胞中营养感测的模型,因此该系统的有效算法的开发可应用于高等真核生物(包括人类)中的信号转导途径的映射。这一研究领域的进展将直接加强和补充科学界的许多技术,同时产生宝贵的国际伙伴关系。 CMB在真核微生物的代谢工程、发酵、生理学、功能基因组学和系统生物学方面具有很强的国际地位。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Michael Jewett其他文献
1182 GROWTH KINETICS OF SMALL RENAL MASSES: A PROSPECTIVE ANALYSIS FROM THE RENAL CELL CARCINOMA CONSORTIUM OF CANADA
- DOI:
10.1016/j.juro.2013.02.2536 - 发表时间:
2013-04-01 - 期刊:
- 影响因子:
- 作者:
Michael Organ;Michael Jewett;Mohamed Abdolell;Joan Basiuka;Neil Fleshner;Antonio Finelli;Christopher Morash;Stephen Pautler;Joseph Chin;Robert Siemens;Simon Tanguay;Martin Gleave;Darrel Drachenberg;Raymond Chow;Andrew Evans;Brenda Gallie;Masoom Haider;John Kachura;Ricardo Rendon - 通讯作者:
Ricardo Rendon
1476 PATIENTS WITH NON PRIMARY PT1 NON-MUSCLE INVASIVE BLADDER CANCER (NMI-BC) TREATED WITH BACILLUS CALMETTE-GUERIN (BCG) ARE AT HIGHER RISK OF PROGRESSION COMPARED TO PRIMARY T1 TUMORS
- DOI:
10.1016/j.juro.2010.02.1191 - 发表时间:
2010-04-01 - 期刊:
- 影响因子:
- 作者:
Sultan Alkhateeb;Bas Van Rhijn;Antonio Finelli;Theodorus van der Kwast;Andrew Evans;Sally Hanna;Rati Vajpeyi;Neil Fleshner;Michael Jewett;Alexandre Zlotta - 通讯作者:
Alexandre Zlotta
MP28-12 MOLECULAR MARKERS (FGFR3 MUTATION; P53 & KI-67 EXPRESSION) AND CLINICAL OUTCOME OF RADICAL CYSTECTOMY FOR BLADDER CANCER: A MULTICENTER, MULTILAB STUDY
- DOI:
10.1016/j.juro.2014.02.661 - 发表时间:
2014-04-01 - 期刊:
- 影响因子:
- 作者:
Laura Mertens;Tahlita Zuiverloon;Yann Neuzillet;Shahrokh Shariat;Cheno Abas;Peter Bostrom;Marcel Vermeij;Tuomas Mirtti;Arthur Sagalowsky;Joost Boormans;Dennis Peters;Raheela Ashfaq;Jeroen de Jong;Annegien Broeks;Neil Fleshner;Simon Horenblas;Arno van Leenders;Bharati Bapat;Michael Jewett;Alexandre Zlotta - 通讯作者:
Alexandre Zlotta
1677 NATURAL HISTORY OF RENAL FUNCTION IN UNTREATED KIDNEY CANCER
- DOI:
10.1016/j.juro.2012.02.1550 - 发表时间:
2012-04-01 - 期刊:
- 影响因子:
- 作者:
Ashraf Almatar;David Margel;Antonio Finelli;Hannah Chung;Neil Fleshner;Alexandre Zlotta;Laura Legere;Henry Ajzenberg;Michael Jewett - 通讯作者:
Michael Jewett
MP40-02 INCREASED UPTAKE OF RENAL TUMOUR BIOPSIES FOR SMALL RENAL MASSES – RESULTS OF A MULTICENTRE CANADIAN EXPERIENCE
- DOI:
10.1016/j.juro.2014.02.1337 - 发表时间:
2014-04-01 - 期刊:
- 影响因子:
- 作者:
Jaimin R. Bhatt;Simon Tanguay;Zhihui Liu;Patrick O. Richard;Anil Kapoor;Ricardo Rendon;Louis Lacombe;Peter Black;Stephen Pautler;Rodney Breau;Ronald Moore;Michael Jewett;Antonio Finelli - 通讯作者:
Antonio Finelli
Michael Jewett的其他文献
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{{ truncateString('Michael Jewett', 18)}}的其他基金
Collaborative Research: Cell-free glycoprotein synthesis technology for point-of-care vaccine biomanufacturing
合作研究:用于即时疫苗生物制造的无细胞糖蛋白合成技术
- 批准号:
2341123 - 财政年份:2023
- 资助金额:
-- - 项目类别:
Continuing Grant
Collaborative Research: Cell-free glycoprotein synthesis technology for point-of-care vaccine biomanufacturing
合作研究:用于即时疫苗生物制造的无细胞糖蛋白合成技术
- 批准号:
1936789 - 财政年份:2020
- 资助金额:
-- - 项目类别:
Continuing Grant
Collaborative Research: Repurposing the translation apparatus for mirror image polypeptide synthesis
合作研究:重新利用镜像多肽合成的翻译装置
- 批准号:
1716766 - 财政年份:2017
- 资助金额:
-- - 项目类别:
Standard Grant
Synthetic Biology, Engineering, Evolution & Design 2016 (SEED 2016), Chicago, IL, July 18-21, 2016
合成生物学、工程学、进化论
- 批准号:
1634295 - 财政年份:2016
- 资助金额:
-- - 项目类别:
Standard Grant
Collaborative Research: Glycoengineering Without Borders: Bacterial Cell-Free Glycoprotein Synthesis
合作研究:无国界糖工程:细菌无细胞糖蛋白合成
- 批准号:
1413563 - 财政年份:2014
- 资助金额:
-- - 项目类别:
Standard Grant
Materials World Network: Chemical and BIological Approaches to Sequence Controlled Polymers
材料世界网络:序列控制聚合物的化学和生物方法
- 批准号:
1108350 - 财政年份:2011
- 资助金额:
-- - 项目类别:
Continuing Grant
Collaborative Research: Engineering Genetically Augmented Polymers (GAPS)
合作研究:工程基因增强聚合物 (GAPS)
- 批准号:
0943393 - 财政年份:2009
- 资助金额:
-- - 项目类别:
Standard Grant
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- 批准号:10774081
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- 项目类别:面上项目
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