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国自然单细胞项目申请 | 你的摘要够好吗？
标书的项目摘要求在400字（包含标点符号）以内，一般需要包括六个要素：1）研究背景和进展，2）亟待解决的问题，3）申请人前期的工作基础，4）项目的科学假说，5）为验证该假说需要展开的研究，6）该研究的意义。以上六部分不一定全出现，遗漏一两项也可能出现。摘要写作被称为是一种“八股文”写作，常用的模式是：针对…背景（需求、问题），提出…方法（理论），研究…内容，采用…路线（方法、技术途径），解决…科学问题，达到…目标，有…创新点（重要意义）。也可以把摘要概况为5句话。第一句简要讲清楚你的研究项目涉及的疾病及其危害、或者某种自然现象，让评审人知道你的研究项目和啥有关系；第二句过渡到这个领域中存在的一个科学问题，即告诉评审人你的项目就是要解决这个非常重要的科学问题；第三句告诉针对这样的科学问题你已经取得的发现或者初步结果，这些前期工作基础是支持你进一步来解决该科学问题；第四句告诉评审人你将提出下面3-4点研究内容来解决该科学问题；你可以列出这3-4点精炼的研究内容；第五句纯粹是客套话，就是解决的该科学问题带来的科学和社会意义或者价值。可以看到，摘要基本涵盖了标书里面最重要的信息，给足了项目是否资助的判断标准。因此，流传着这样的说法，当看到一份标书的摘要的时候就基本知道这份标书能否获得资助了。
最后再提醒，摘要一定要做多轮修改，一定一定一定要打印出来看，有些问题是电脑上看不出来的，专家看的也是纸质申请书。
下面我们来看3份获批的单细胞项目标书的中英文摘要，大家来仔细地品一品，他们是怎样介绍摘要的六要素的，哪些描述值得借鉴。
项目名称：利用单细胞转录组分析技术对肿瘤内部异质性的系统研究
项目类别：面上项目
研究期限：2015-01-01 至 2018-12-31
肿瘤内部细胞之间具有高度的异质性。对该异质性的深入研究有望为理解肿瘤的发生发展、转移、药物敏感性等疾病过程提供重要信息。本项目将以肝细胞癌为例，使用最新的单细胞分析技术，对肿瘤内部单细胞进行转录组分析。以此为基础，我们将确定该组细胞中的细胞亚群，及各细胞亚群的标志性基因，从而首次提出肿瘤异质性在单细胞转录组层次的详细图谱。其次，我们将采用肿瘤系统生物学的方法，使用单细胞转录组数据构建该肝细胞癌的基因转录调控网络。对该转录调控网络及单细胞转录组数据的进一步深入分析将提出各肿瘤细胞亚群区别于正常及其它肿瘤细胞的核心转录调控因子。最后，我们将通过实验分析手段，研究各细胞亚群的功能表型差异，并验证其核心转录调控因子对细胞功能表型的调控作用。总之，本项目首次从单细胞转录组角度系统研究肿瘤内部异质性，为该肝细胞癌中细胞的起源与发展提供机理性信息，并为其它单细胞层次的肿瘤机理研究提供数据及方法上的支持。
英文摘要
Intra-tumoral cell populations display remarkable heterogeneity, which is both cause and consequence of tumor initiation and progression. Therefore a comprehensive view on intra-tumoral heterogeneity should provide valuable information for understanding important cancer-related processes such as tumor development, metastasis, drug sensitivities, etc. Traditional high-throughput profiling techniques provide snapshots of molecular species' abundance averaged on thousands to millions of cells, therefore falling short of capturing the heterogeneous nature of tumors. The recently developed single-cell techniques now allow comprehensive transcriptome profiling for a large number of single-cells. In the proposed research, we plan to take advantages of the most advanced single-cell transcriptome profiling technique, and systematically study the intra-tumoral heterogeneity of a hepatocellular carcinoma (HCC) case as an example. The project includes the following major steps: 1) data collection. We will collect tumor single-cells from a HCC model, and perform transcriptome profiling to obtain mRNA expression profiles of single-cells. 2) data analysis. We will perform statistical analyses such as 2-dimensional hierarchical clustering and principle components analysis. This will cluster the single-cells into transcriptionally distinct sub-populations, and identify their signature genes. We will also apply systems biology methodologies to reconstruct the gene transcriptional regulation network, using the single-cell gene expression data. 3) network and transcriptome profile analysis. We will further use the gene transcriptional regulatory network to dissect the transcriptome profiles of the single-cell sub-populations and infer their master regulators that transcriptionally drive the phenotypic differences between cell sub-populations. 4) experimental validations. We will isolate the single-cell sub-populations, and assess their phenotypic differences such as proliferation, migration, invasion, and in vivo tumorigenesis. We will also validate the involvements of master regulators in driving the differences between the cell sub-populations. The proposed research will yield very valuable results: 1) the first large-scale HCC single-cell transcriptome profiles. 2) a novel intra-tumor cell map composed of single-cells clustered based on their gene expression profiles. 3) the first personalized regulatory network to capture the gene transcriptional regulatory machineries that are derived from one case of cancer. 4) key transcription factors that drive the phenotypic differences between cell sub-populations. In summary, by systematically interrogating intra-tumoral heterogeneity, the proposed research will provide, for the first time, a valuable basis of data, methodology, and preliminary mechanistic information for further research on patient-specific cancer mechanisms and potentially for the development of personalized medicine.
肿瘤干细胞在结直肠癌的形成、转移和复发中扮演重要角色。前期工作中我们通过对结直肠癌EpCAM(high)CD44(+)及EpCAM(high)Lgr5(+)肿瘤干细胞进行单细胞基因组测序发现，不同患者肿瘤干细胞的基因拷贝数变异模式具有个体特异性，同一患者用相同标志物分选的肿瘤干细胞具有不同的基因拷贝数变异模式，即具有异质性。本项目拟在此基础上，探索结直肠癌肿瘤干细胞在基因组和表达层面的特异性及异质性。首先应用单细胞基因组测序技术，探索不同患者基因组拷贝数变异的个体特异性，深入分析同一患者肿瘤干细胞亚群之间的进化关系。然后根据单细胞转录组测序数据得到基因表达谱信息，探究不同肿瘤干细胞之间基因表达的异质性。在此基础上以特定表达的基因为依据，对单细胞进行聚类分析。最后结合临床资料，初步探索不同肿瘤干细胞亚群与肿瘤基因分型的关系。上述研究将为阐明结直肠癌肿瘤干细胞的异质性及其临床相关性奠定基础。
英文摘要
Cancer stem cell (CSC) plays an important role in the development of colorectal cancer. Colorectal CSCs can be isolated with cell surface markers including EpCAM(high)CD44(+) and EpCAM(high)Lgr5(+), etc. Recently, we have analyzed the genome of single cells isolated by these two sets of biomarkers via single cell whole genome sequencing, and our preliminary data suggest that 1) each colorectal tumor in general follows a common copy number variation (CNV) pattern; while 2) CSCs expressing the same surface marker from the same tumor could have more than one CNV patterns, indicating its heterogeneity. This project aims to investigate the genomic variation and transcriptome heterogeneity of CSCs purified with EpCAM(high)CD44(+) and EpCAM(high)Lgr5(+). We will first analyze the relationship between different CSC subpopulations during tumor revolution by single cell whole genome sequencing. And then determine the heterogeneous gene expression pattern of CSCs via single cell transcriptome sequencing, and perform hierarchical clustering according to certain genes. Finally, we will explore the correlation of CSC subpopulations with colorectal cancer genotype classification. This study will shed light on understanding CSC heterogeneity and its clinical relavance.
造血微环境结构和功能异常导致造血抑制是骨髓衰竭性疾病的主要病理机制，BM-MSCs成骨/成脂定向分化失衡是其造血支持功能缺失的关键环节。本室前期研究显示，成脂诱导后，部分BM-MSCs并不触发成脂而表现出成脂抵抗。细胞亚克隆分析显示该群细胞上触发早期成脂分化的C/EBPβ基因表达显著降低，提示其在BM-MSCs上的异质性表达导致成脂抵抗，但对其进行调控的上游信号通路不明。传统方法只能检测细胞群体的基因表达平均水平，无法精准确定对C/EBPβ进行调控的上游调节蛋白及二者的确切关系。本项目拟应用一种新的微流体单细胞基因检测技术，筛选差异性表达C/EBPβ的BM-MSCs，行单细胞基因测序结合细胞生物信息学分析，确定成脂抵抗BM-MSCs上调控C/EBPβ的关键蛋白及信号通道，阐明BM-MSCs差异性表达C/EBPβ影响其成脂分化的分子机制，为成脂分化异常所致骨髓衰竭性疾病的临床救治提供新思路。
英文摘要
Hematopoietic suppression caused by structural changes and dysfunction of hematopoietic micro-environment is the main pathological mechanisms of bone marrow failure disorders in patients, such as acute hematopoietic radiation syndrome. Bone marrow mesenchymal stem cells (BM-MSCs) play a crucial supporting role in hematopoiesis by maintaining the balance between adipogenic and osteogenic differentiation. Our previous studies suggested that after adipogenic induction, part of a cell does not trigger the adipogenic differentiation, in which showed adipogenic resistance. Cell sub-clone analysis showed that the expression of the C/EBPβ gene decreased significantly in those cells, which suggesting that C/EBPβ might be a key molecule involved in adipogenic resistance. However, the molecular mechanism of this pathway remains elusive. Traditional methods could only detect average gene expression level of cell population, but could not accurately determine the exact relationship between the upstream regulator and C/EBPβ.This study aims to screen the single BM-MSCs which could heterogeneous expressed C/EBPβ, analyse and screen the key signal channel regulator of C/EBPβ which related to the adipogenic resistant BM-MSCs through the nano micro fluid single cell platform technique combined with analysis of cell biological information, clarify the molecular mechanism of heterogeneous expression of C/EBPβ in BM-MSCs would influence its adipogenic differentiation. We would provide a new idea for the clinical treatment of bone marrow failure diseases induced by abnormal adipogenic differentiation.最后，强烈推荐你阅读我们首发的《单细胞测序工具书》，你需要的国自然单细胞项目申请材料统统都在这本书里。
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