穆罕默德-R-塞德萨亚姆多斯特 生物化学家

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Mohammad R. Seyedsayamdost
Biological Chemist | Class of 2020
Investigating synthesis of novel molecules with therapeutic properties and expediting discovery of new antibiotics.


Portrait of Mohammad R. Seyedsayamdost

Title
Biological Chemist
Affiliation
Department of Chemistry, Princeton University
Location
Princeton, New Jersey
Age
41 at time of award
Area of Focus
Biochemistry, Biophysics, and Structural Biology, Chemistry
Website
The Mo Lab
Princeton University: Mo Seyedsayamdost
Published October 6, 2020
ABOUT MOHAMMAD'S WORK
Mohammad R. Seyedsayamdost is a biological chemist investigating the synthesis of new small molecules with bioactive or therapeutic properties. Nearly 70 percent of clinically used antibiotics (e.g., penicillin) are natural products or natural product derivatives generated by biosynthetic pathways in bacteria and fungi. The molecules, or secondary metabolites, from most of these pathways are only synthesized under certain conditions, which are difficult to replicate in typical laboratory cultures.

Leveraging commercially available libraries of small molecules (oftentimes known antibiotics), Seyedsayamdost developed a method called HiTES (High-Throughput Elicitor Screening) that can rapidly activate otherwise silent (or cryptic) secondary metabolic pathways and, therefore, production of the corresponding natural products. He then uses a range of methods, including nuclear magnetic resonance spectroscopy, computational and analytical chemistry, and imaging mass spectrometry to analyze and characterize the structure (and potential uses) of these complex natural products. Seyedsayamdost has also discovered novel naturally occurring compounds in symbiotic interactions that often emerge in environments with extensive microbial diversity. For example, he determined the mechanisms by which marine Roseobacter bacteria interact with microalgae using natural products. The interaction is usually beneficial; however, when the microalgae begin to deteriorate, cryptic gene clusters in the Roseobacter trigger synthesis of toxic secondary metabolites that kill the microalgae and ensure the survival of the Roseobacter. Over the course of these and other investigations, his group has identified a variety of molecular structures with unusual bond patterns, suggesting a rich and diverse set of biochemical pathways that might be useful for producing additional compounds. In recent work, Seyedsayamdost elucidated the formation of intramolecular crosslinks needed to impart the unique structure and bioactive characteristics of vancomycin, an antibiotic of last resort against persistent infections. He also established a combined synthetic/enzymatic approach to expedite discovery of antibiotics that are similar to vancomycin but can remain effective against vancomycin-resistant infections.

As new infectious diseases emerge and pathogenic bacteria develop resistance to our current arsenal of antibiotic treatments, Seyedsayamdost’s research is expanding the toolbox available to synthetic organic chemists and opening up access to a new trove of previously unknown and potentially therapeutic biochemical compounds.

BIOGRAPHY
Mohammad R. Seyedsayamdost received combined BS/MS (2001) degrees from Brandeis University and a PhD (2008) from the Massachusetts Institute of Technology. He was a postdoctoral fellow at Harvard Medical School prior to joining the faculty of Princeton University in 2013, where he is currently an associate professor in the Department of Chemistry. He also holds appointments in the Princeton Environmental Institute and the Woodrow Wilson School of Public and International Affairs. Seyedsayamdost’s scientific research has been published in such journals as Nature Chemistry, Nature Chemical Biology, Journal of the American Chemical Society, PNAS, and mBio, among others.

IN MOHAMMAD'S WORDS
MohammadSeyedsayamdost:"Bacteriacommunicateusingalanguageconsistingofsmallmolecules,withthemoleculesrepresentingwordsandtheirfunctionsconveyingmeaning.Wehaverecentlylearnedthatbacteriaemploymuchlargersmallmoleculevocabulariesthanpreviouslyanticipated."


Communication is essential, even for primitive bacteria that dwell in soil, the human gut, or other habitats. Bacteria communicate using a language consisting of small molecules, with the molecules representing words and their functions conveying meaning. This chemical language is important because it provides insights into a critical component of microbial physiology, because it affords a tool with which to control bacterial behavior, and because it is the source of about 70 percent of all clinical antibiotics. We have recently learned that bacteria employ much larger small molecule vocabularies than previously anticipated. Devising creative approaches to tap into this vast chemical scape, and investigating the biosynthesis, functions, and possible therapeutic uses of the corresponding molecules, provide the main motivations for my research.



穆罕默德-R-塞德萨亚姆多斯特
生物化学家 | 2020级
研究具有治疗特性的新型分子的合成，加快发现新的抗生素。


穆罕默德-R-赛义德萨姆多斯特的肖像
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标题
生物化学家
工作单位
普林斯顿大学化学系
工作地点
普林斯顿，新泽西
年龄
获奖时41岁
重点领域
生物化学、生物物理学和结构生物学, 化学
网站
莫氏实验室
普林斯顿大学。莫-塞德萨伊姆多斯特
2020年10月6日发布
关于Mohammad的工作
Mohammad R. Seyedsayamdost是一名生物化学家，研究具有生物活性或治疗特性的新小分子的合成。近70%的临床使用的抗生素（如青霉素）是由细菌和真菌的生物合成途径产生的天然产物或天然产物衍生物。这些途径中的大多数分子或次级代谢物只在特定条件下合成，而这些条件在典型的实验室培养物中很难复制。

利用商业上可获得的小分子库（通常是已知的抗生素），Seyedsayamdost开发了一种名为HiTES（高通量诱导剂筛选）的方法，可以快速激活其他沉默的（或隐蔽的）次级代谢途径，从而生产相应的天然产品。然后，他使用一系列的方法，包括核磁共振光谱、计算和分析化学以及成像质谱，来分析和描述这些复杂的天然产品的结构（和潜在用途）。Seyedsayamdost还在共生互动中发现了新的自然发生的化合物，这种互动往往出现在具有广泛微生物多样性的环境中。例如，他确定了海洋玫瑰杆菌与微藻类利用天然产品进行互动的机制。这种互动通常是有益的；然而，当微藻开始恶化时，玫瑰菌中的隐性基因簇会触发有毒次级代谢产物的合成，从而杀死微藻并确保玫瑰菌的生存。在这些和其他调查的过程中，他的小组已经确定了各种具有不寻常键型的分子结构，表明有一套丰富多样的生化途径，可能对生产更多的化合物有用。在最近的工作中，Seyedsayamdost阐明了万古霉素的独特结构和生物活性特征所需的分子内交联的形成，万古霉素是对付顽固性感染的最后一种抗生素。他还建立了一种综合的合成/酶学方法，以加快发现与万古霉素相似但能保持对万古霉素耐药性感染有效的抗生素。

随着新的传染病的出现和致病菌对我们目前的抗生素治疗库产生抗药性，Seyedsayamdost的研究正在扩大合成有机化学家可用的工具箱，并打开了获得以前未知和潜在的治疗性生化化合物的新宝库。

个人简历
Mohammad R. Seyedsayamdost在布兰代斯大学获得学士/硕士（2001年）学位，在麻省理工学院获得博士学位（2008年）。在2013年加入普林斯顿大学之前，他是哈佛大学医学院的博士后研究员，目前是该校化学系的副教授。他还在普林斯顿环境研究所和伍德罗-威尔逊公共和国际事务学院担任职务。Seyedsayamdost的科研成果已发表在《自然-化学》、《自然-化学生物学》、《美国化学会杂志》、《美国科学院》和《mBio》等杂志上。

默罕默德的话
穆罕默德-赛义德说："细菌使用由小分子组成的语言进行交流，小分子代表单词，其功能传达意义。


交流是必不可少的，即使是居住在土壤、人类肠道或其他栖息地的原始细菌。细菌使用一种由小分子组成的语言进行交流，分子代表单词，其功能传达意义。这种化学语言非常重要，因为它提供了对微生物生理学的一个重要组成部分的洞察力，因为它提供了一个控制细菌行为的工具，还因为它是所有临床抗生素的大约70%的来源。我们最近了解到，细菌使用的小分子词汇量比以前预期的要大得多。设计创造性的方法来开发这个巨大的化学领域，并研究相应分子的生物合成、功能和可能的治疗用途，是我研究的主要动机。