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博士屯教育 | 从加州到耶鲁,我参加美国科研

发表时间:2020-03-29

秉持尊重学生和家长隐私的原则,以下所展示的信息,已经去掉敏感和涉及知识产权的信息。

还有N多学术素材,由于知识产权或家长原因,不便公开,敬请理解。

本文作者Y同学,来自加州的私立高中,托福110,SAT1570,四项AP课程获得A类成绩。祖籍上海,小学毕业后移民到美国。爸爸妈妈对于孩子的期盼是接受更好的大学教育,有更好的未来。

Y同学对于生物体的调节、基因的表达背后复杂的生理机制非常感兴趣,希望自己能够在生物研究方面有所建树。对于大学申请,他想能够按照自己的兴趣选择生物相关的专业。申请美国名校,往往都需要美国本土的科研经历和对应的教授推荐信。但是,作为一名高中生,能够接触到的生物相关的专业知识以及实验操作技能是匮乏的。一般而言,顶尖的美国私立中学,生物实验室的设备也是只能适合中学基础层次的学习。为了能够获得生物相关的经验和实验技能,达到梦想大学的录取要求,Y同学报名了参加美国名校科研的选拔。参加美国名校科研,增加学术背景,开拓视野,获得真知。经过美国哈佛大学教授面试,Y同学顺利获得科研录取名额。

在科研项目结束后,我们很高兴看到教授对于Y同学的评价中写道:“他非常勤奋,表现出出色的自学能力,细心,诚实,友善,对于学习新的研究技能和新知识表现出强烈的渴望。”(He demonstrated great diligence, wonderful self-learning skills, carefulness, honesty, friendship and strong desire to lean new research skill and new knowledge.)

在科研结束后的大学申请环节,结合高中阶段良好的GPA,理想的SAT成绩,及科研履历和教授推荐信,Y同学如愿以偿的获得了耶鲁大学的录取。作为科研申请老师,我们内心祝福孩子获得了极度理想的录取结果。同时,我们深深的知道,耶鲁大学的录取,不仅仅是科研履历和教授推荐信的结果,还和学生本身的其他条件息息相关,是学生本人,家庭,以及所有留学老师共同努力的结果。

作为科研申请老师,我们对Y同学能够在学业上取得进步感到自豪,同时我们也想告诉每位参与美国科研的孩子,获得推荐信、科研证书、科研报告、科研履历,其实仅仅是美国科研的基础性收获。更为重要的是,学生可以通过与顶尖学者、教授的交流,树立了长期的学术目标,让学术能力伴随着生命的成长而发展,让学术赞美生命!

美国科研就是背景提升,目标就是提高本、硕、博录取质量。

科研总结(节选)

本文是学生在美国大学科研学习结束后所写的感受,并在文后附录了学生的推荐信、参与科研选拔面试前的作业、科研面试后的教授面试报告,供其他学生及家长爸爸妈妈们参考。

注:中文译文是编辑进行的整理,英语能力较好的学生和家长建议直接阅读英文。

Week 1

To put it fairly, I did my part of the research several days before the research program. Being a “literal” molecular biology enthusiast and having taken solely an introductory chemistry course, I have little knowledge on the operation of lab logistics and equipments. As I dived into waves of new information, slightly overwhelmed, a picture of what’s to come began to form vaguely.

几乎可以说,我在科研开始的前几天就完成了一部分研究工作。作为分子生物学爱好者并且只参加过化学入门课程,对于实验室运行和设备的操作了解甚少。当我开始进入新知识浪潮中时,我有点不知所措,但对于将要发生的隐约知道。

Thanks to my prior information, the instruction session on the first day came to me as extremely smooth. As a review of the fundamentals of HPLC, the lecture strengthens my understanding of the separation device. Put it simply, it establishes a platform for me to understand the principles the equipment is set on.

多亏之前的了解,第一天的讲授对我来说非常顺利。作为对HPLC基础知识的回顾,讲授加深了我对分离装置的理解。简而言之,它为我建立了一个了解设备所基于原理的平台。

Notes:

-HPLC as separation deviceHPLC分离装置

-Interaction between stationery phase and mobile phase固定相和流动相之间的相互作用

-reverse and normal phase - selected as appropriate (polarity) 反相和正相-适当选择(极性)

…………

…………

When it came to operation, everything gets elevated to a whole new level however. I have probably admitted 10 times that my lab experience prior to the program is zero to none, so this is absolutely new for me. Putting on the lab coat and being involved in an experiment is a joy - as if playing one of those “pretend” game that I used to play where I was a doctor when I was young. However, the operation protocols were soon minded after a few tries, I can stumble my way across the whole preparation startup calibration injection process.

在投入使用后,一切都提升到了一个全新的水平。在科研进行前,我可能多次说明我的实验室经验是无,所以这对我来说绝对是全新的体验。穿上实验服做实验是一种乐趣,好像是小时候玩的假扮医生的游戏。虽然操作几次后,记住了操作流程,但是在整个操作起始的校准注入的时候遇到了阻碍。

Notes:

-Startup - detector longest time needed检测器启动需要很长时间

-Water run through gradually change flow rates逐渐改变水流速

-Calibration校准

…………

…………

Overall, a very productive week - exhausting as well, but I am very glad to see that I am learning actively and was familiarized with HPLC Operation and standard lab prep.

总体而言,这是一个非常有成效的一周虽然很辛苦,但我很高兴看到我积极性高地学习并且熟悉HPLC操作和标样的制备。

Week 2

This week is primarily spent on the preparation of buffer, sample, as well as training on the standard Western Blot protocols. I focused on getting familiar with various procedures and understanding the performance of the error and adjustment process in the second week of time. Together in the two weeks, I observed and performed fundamental biology lab techniques for which integration would ensue successful research. I also tried to do some extension reading that would help me with comprehending the biological processes.

这周主要用于缓冲液、样品的制备以及标准Western Blot印迹的培训。第二周,我专注于熟悉各种操作,明白操作出现的错误和如何调整。在这两周的时间里,为了能够研究成功,我观看并进行了基础生物学实验室技术操作。我还尝试做一些扩展阅读,以帮助我理解生物学过程。

Notes:

-Buffer preparation缓冲液制备

- Stoichiometry (calculation) 化学计量(计算)

- dilution & sample preparation 稀释和样品制备

- pH measurement technology PH测试

- Standard lab skills 标准实验技能

…………

…………

Week 3&Week 4

These two weeks are primarily focused on the performance of protein concentration detection assays and the processing of complex data results. Through experimenting with different techniques commonly used in labs (including protein assays, HPLC, creatine assays etc) , I experienced various approaches to the determination of the concentration of specific proteins presented in the mice hearts. The data gathered allowed us to analyze the differences in the concentration of metabolites/catabolites between the ischemia perfused and normal heart tissues in details.

这两个星期主要集中在蛋白质浓度检测分析的操作和复杂数据结果的处理上。通过试验实验室中常用的不同技术(包括蛋白质测定,HPLC,肌酸测定等),我进行了各种测定小鼠心脏中特定蛋白质浓度的方法的实验。收集的数据使我们能够详细分析局部缺血和正常心脏组织之间代谢产物/分解代谢物的浓度差异。

For me, the most important aspect of the research program is the experience gained to be able to weave different techniques into a complete research pathway. Starting with the HPLC running results giving the area estimates, we derived the amount of metabolites presented in each injection using the predetermined standard curves. Through gathering the total protein concentration in the 2 samples, the total amount of proteins presented in each of the ischemia perfused and normal heart tissue is determined. Using such relation, we were able to calculate the amount of metabolites presented in each unit of the protein, which is later being used to contrast the differences in metabolite concentration under 2 conditions.

对我而言,科研最重要的方面是获得的科研经验,能够将不同的技术组合成完整的研究路径。从给出面积估计值的HPLC运行结果开始,我们使用预定的标准曲线得出了每次注射中存在的代谢物的量。通过收集2个样品中的总蛋白浓度,可以确定每个局部缺血和正常心脏组织中存在的蛋白总量。利用这种关系,我们能够计算出蛋白质每个单元中存在的代谢物的量,随后将其用于对比两种条件下代谢物浓度的差异。

Being able to integrate the fundamental techniques is the basis for success as being a part of the complex experimental roadwork. As one of the guiding principles in the biological field, applying techniques fittingly often can yield clear logic.

能够将基本技术集成是成功的基础,因为它是复杂实验性工作的一部分。作为生物学领域的指导原则之一,经常适当地应用技术可以产生清晰的逻辑。

Notes:

-Sample preparation with animal organ动物器官的样品制备

Homogenization均质化

Pulverization破碎

-Total Protein Assay using Lowry method使用Lowry方法进行总蛋白测定

…………

…………

推荐信(节选)

…….……..

He demonstrated great diligence, wonderful self-learning skills, carefulness, honesty, friendship and strong desire to lean new research skill and new knowledge. He is a quick learner and very good at taking notes. As a research scientist with many years of advising experiences, I can say for sure that he is a kind of student that most university would love to have. He has cheerful attitude and very good communication skills. He is very self-motivated, optimistic, thoughtful and compassionate. He is a sharp student who presents high potential. I am confident that he will be an excellent student if he is granted the opportunity.

他非常勤奋,表现了出色的自学能力,细心,诚实,友善,对于学习新的研究技能和新知识表现出强烈的渴望。他学习速度很快,擅长做笔记。作为具有多年咨询经验的研究科学家,我可以肯定地说,他是大多数大学都希望拥有的那种学生。他开朗,善于沟通。他非常有上进心、乐观,体贴和有同情心。他是一个很有潜力的聪明学生。我有信心,只要有机会,他就会成为一名出色的学生

教授面试报告(节选)

Dear D,

I introduced our equipment, animal models and ongoing experiments and to Y. We possess 25 pieces of functional equipments, including NMR (nuclear magnetic resonance) and HPLC (high performance liquid chromatography). We have successfully developed several animal disease models including ………….

我向Y介绍了我们的仪器,动物模型和正在进行的实验。我们拥有25台功能性仪器,包括NMR(核磁共振)和HPLC(高效液相色谱)。我们已经成功研究了几种动物疾病模型,…………。

Y told me that as a high school student, he has to admit that his knowledge on the subject, especially on experimental techniques, is extremely limited. He wants to learn some of them.

Y告诉我,作为一名高中生,他必须承认他对这一课题的知识,特别是对实验技能的知识极为有限。为此,他想学习对其进行学习。

I told Y learning through doing. As #1 University all over the world, Harvard has been leading scientific research for many years. Y told me that he will get some senses on Harvard environment by attending a research program. I believe that this research program will help Y explore the possibility to become a researcher in biological sciences and this experience will give him a chance to realize his true passion.

我告诉Y可以边做边学。作为全球排名第一的大学,哈佛多年来一直引领科学研究。Y告诉我,他将通过参加一个科研项目对哈佛的环境有所了解。我相信这个项目将帮助Y探索成为生物科学研究者的可能性,而这种经验将使他有机会实现自己的真正热情。

In my impression, Y’s English skills are at a pretty high level, his course GPA is excellent, He has finished four AP courses at Grade A. If he can finish additional AP courses, earn more volunteer hours and Strengthen sports or leadership in his grade 11, he will be a strong candidate for Ivy League.

在我的印象中,Y的英语水平相当高,他的GPA课程非常出色,他已经完成了四门A级AP课程。在11年级中,如果他可以完成更多的AP课程,获得更多的志愿者时间,并且可以提高自己的成绩或领导能力,他将成为常春藤联盟的有力候选人。

…………

…………

面试前学生准备

Epigenetics & Epigenomic Variation

Epigenome. Frankly, while I am quite confident about my knowledge on fundamental genetics, I have never been acquainted with the terminology before. Being greatly interested, I dived into frantic research.

坦白说,尽管我对基本遗传学知识很有信心,但我之前对表观基因组并不熟悉。凭借着强烈的兴趣,我投入了疯狂的研究。

Epigenetics, to my understanding, is the change in gene expression without any modifications in the DNA itself - in short, a change in phenotype without changes in genotype. While genome defines the DNA, epigenome defines how the gene is expressed. Environmental factors, such as stress, contamination, and behavior are all capable of altering the epigenome, which leads to mistaken gene expression that can lead to disorders. Thus, it is strongly suggested that epigenome changes throughout life based on individual-specific choices.

基因在转录和翻译成蛋白质时会表达,这可能会受到表观遗传学变化的影响。在此过程中,细胞的表观基因组由附着在DNA或组蛋白复合物上的化学标签所赋予,可以影响特定基因的表达和抑制,进而改变表型行为。

One of the process commonly involved in the epigenetic modifications is methylation. Binded to CpG sites, methyl groups act as gene expression controls and are often associated with gene silencing (carried out by DNMT enzymes). They also contribute to the differentiation and specialization of cells (epigenetic modification), given that all cells have identical DNA. In addition, histone modification is often another type of alternation involved. In this case, tags are added directly to histone tails which in turn modifies gene expression. Examples include H3K9 (transcription activation) & H3K27 (transcription suppression). Gene expression is directly controlled by the epigenome of individuals.

通常涉及表观遗传修饰的过程之一是甲基化。甲基与CpG位点结合,可以作为基因表达对照组,这通常与基因沉寂相关(由DNMT酶进行)。考虑到所有细胞都具有相同的DNA,它们还有助于细胞的分化和专化(表观遗传修饰)。另外,组蛋白修饰通常是涉及的另一种类型的交替。在这种情况下,将标签直接添加到组蛋白尾巴上,从而修饰基因表达。示例包括H3K9(转录激活)和H3K27(转录抑制)。 基因表达直接受个体的表观基因组控制。

…………

…………

Thus, from what I understand from my search, it is unsurprising for each person to have a distinct pattern in phenotype, yet the delicate mechanism behind this variation is still greatly ambiguous. The review, “Genetic Sources of Population Epigenomic Variation”, establishes interesting insights in the unveiling the patterns, factors and mechanisms of epigenomic variation that leads to phenotypic diversity.

因此,从我的搜索中了解到,每个人的表型都有独特的模式并不奇怪,但是这种变化背后的微妙机制仍然非常模棱两可。这篇综述《种群表观基因组变异的遗传源》在揭示导致表型多样性的表观基因组变异的模式,因素和机制方面建立了有趣的见解。

In the research, researchers primarily introduce the use of chromatin state map as an agent to explore the functionality and workings of the epigenome in details. Aided by the development of NGS measurements, chromatin state map defines a presence/absence structure of genome-wide measurements of different epigenetic marks, and therefore provides an “operational definition for epigenome” (319) and makes it easier for any “comparison across tissues, developmental stages and individuals” (322).

在这项研究中,研究人员主要介绍了染色质状态图的使用,以详细探索表观基因组的功能和工作原理。借助NGS测量的发展,染色质状态图定义了不同表观遗传标记的全基因组测量的存在/不存在结构,因此提供了“表观基因组的操作定义”(319),并使任何“组织间的比较”、 发展阶段和个人更加容易”(322)。

…………

…………

In addition, researchers presented that cis-regulatory SNPs, which possibly involves mutations in TFBS, and accounts for part of hQTL, is the determining factor in individual differences in DNA methylation and correlation between chromatin states. State transitions, from an enhancer state to a repressive state, represent the convergence of intra and inter-individual epigenomic variation on the same genomic regions (323). In addition to the chromatin states in cis, the states in trans suggest that mutations in trans-acting transcription factors may as well be a source of population epigenomic variation. However, the mutation sets itself apart by displaying “widespread epigenomic dysregulation” and “highly deleterious phenotypes”, as demonstrated by analyses in rats and yeasts. However, based on the results, it is widely suggested that the correlation between in cis and trans acting SNPs and chromatin state variation may explain the heritability of the epigenome at a population level.

此外,研究人员提出,可能涉及TFBS突变并占hQTL一部分的顺式SNP是决定DNA甲基化个体差异和染色质状态之间相关性的决定因素。从增强子状态到抑制状态的状态转换表示同一基因组区域内个体内和个体间表观基因组变异的融合(323)。除了顺式的染色质状态外,反式状态也暗示反式转录因子的突变也可能是种群表观基因组变异的来源。然而,这种突变通过表现出“广泛的表观基因组失调”和“高度有害的表型”而突出,如在大鼠和酵母中的分析所证明的。

In all, the future of the study is unlimited. Current studies, in response to the highly cost prohibitive factor, are restrained by the small population sample. While small scale integrative studies reveal the preliminary effect of the single SNPs on chromatin organizations, it is largely beneficial to scale up the study of chromatin states to include a wider range of subjects, as it would more accurately bolster and elucidate the genetic sources population epigenomic variation with the help of advancing sequencing technologies.

总之,这项研究的未来是无限的。对于成本高昂的限制因素,目前的研究则受到人口较少的限制。虽然小规模的综合研究揭示了单个SNP对染色质组织的初步影响,但扩大染色质状态的研究以涵盖更广泛的受试者范围在很大程度上是有利的,因为在先进的测序技术的帮助下,它将更准确地支持和阐明遗传资源群体的表观基因组学。

…………

…………

选拔流程

1.提交报名表

2.科研组择优面试

3.面试通过后,发送录取确认书

4.协调机票、接机、住宿;

5.赴美开始科研

6.获得导师推荐信,科研证书,丰富的CV、PS履历

学生报名美国名校科研项目的当天,名校科研的后期申请老师会开始面试辅导,并会在未来7天内安排学生与美方大学科研组导师的视频面试。

科研周期

每期时间长度为3—4周;

(针对假期只有2周的申请者,可申请2周实地+2周远程,确保科研收获)

具体情况根据学生面试情况由美方进行调整;

报名后协调安排面试,面试前辅导学生阅读1篇专业论文;



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为了能够获得生物相关的经验和实验技能,达到梦想大学的录取要求,Y同学报名了参加美国名校科研的选拔。 本文是学生在美国大学科研学习结束后所写的感受,并在文后附录了学生的推荐信、参与科研选拔面试前的作业、科研面试…
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