Cause and consequences of multicellularity in Streptomyces

链霉菌是我们最多产的抗生素生产者，代表了一个优秀的，遗传上易于处理的系统来研究细菌的多细胞性。在其营养生长期间，它们以包含横壁的相互连接的多细胞丝的网络存在，横壁将菌丝分隔成隔室，但不导致细胞分裂。丝状形式引起多菌丝菌丝球的形成，其进一步发育成结构化菌落，其中劳动分工决定哪个亚群启动孢子形成以进行繁殖，以及哪个部分的细胞产生抗生素以通过协调的细胞凋亡释放营养保护。然而，分子机制和进化的好处，驱动链霉菌属的多维多细胞性还没有很好地理解，在这个跨学科的建议，协同组合的分子微生物学家和进化生物学家提供了一个独特的可能性，研究分子因素，决定链霉菌多细胞性和分析之间的过渡适应性的好处单细胞和多细胞形态。所提出的研究的分子视角建立在初步抑制分析的基础上，该分析确定了核相关蛋白Lsr2和转录调节因子SsgR是决定从单细胞到多细胞存在的转换的关键因素。通过在实验进化中使用表型操作，将扩展多细胞性的相关分子控制元件的谱。将在资源转换研究和头对头竞争中分析形态和结构对从单细胞到多细胞形态的菌株适应性的影响。我们将量化改变的大小和形态如何影响抗生素的合成和劳动分工，并研究菌丝死亡如何影响细胞内运输。总而言之，我们的专业知识和强大的初步数据相结合，代表了一个独特的强大的基线，以提高我们对细菌多细胞性的遗传学和进化后果的理解。我们还可能揭示操纵多细胞表型的新方法，以提高链霉菌生产的重要工业产品的生产力和多样性，如抗生素和酶，以造福人类。

Streptomyces are our most prolific antibiotic producers and represent an excellent, genetically tractable system to study bacterial multicellularity. During their vegetative growth, they exist as a network of interconnected multicellular filaments containing cross-walls that separate the hypha into compartments but do not lead to cell fission. The filamentous form gives rise to the formation of multi-hyphal mycelial pellets that further develop into structured colonies in which division of labour determines which subpopulation initiates sporulation for reproduction and which fraction of cells produces antibiotics for nutrient protection released by coordinated apoptosis. However, the molecular mechanisms and the evolutionary benefits driving the multi-dimensional multicellularity in the genus Streptomyces are not well understood.In this interdisciplinary proposal, the synergetic combination of a molecular microbiologist and an evolutionary biologist provides a unique possibility to study the molecular factors that determine Streptomyces multicellularity and analyse the fitness benefits of transitions between unicellular and multicellular morphologies. The molecular perspective of the proposed research builds on preliminary suppressor analysis identifying the nucleoid-associated protein Lsr2 and the transcriptional regulator SsgR as key factors that determine the switch from uni- to multicellular existence. The spectrum of relevant molecular control elements of multicellularity will be extended by using phenotypic manipulation in experimental evolution. The effects of form and architecture on fitness of strains with ranging morphologies from uni- to multicellularity will be analysed in resource conversion studies and head-to-head competitions. We will quantify how altered size and morphology affects antibiotic synthesis and labour division and study how hyphal death affects intracellular transport. Altogether, our combined expertise and strong preliminary data represent a uniquely powerful baseline to improve our understanding of genetics and evolutionary consequences of bacterial multicellularity. We may also reveal new approaches to manipulate multicellular phenotypes in order to increase the productivity and diversity of industrially important products made by streptomycetes, like antibiotics and enzymes, for human benefit.