{"title":"高级对话:从基因组到微生物组-一个跨学科的旅程","authors":"Jingyuan Fu","doi":"10.1002/ggn2.202500039","DOIUrl":null,"url":null,"abstract":"<p>My research group, Integrative Omics in Systems Medicine, is affiliated at the University Medical Center Groningen, the Netherlands. Our research aims to understand host-microbe interactions in complex traits and diseases, for which we integrate genetics, microbiome, and large-scale omics data to identify risk factors and their interactions underlying inter-individual variation in disease susceptibility.</p><p>The most pressing challenges lie in the undefined causality and molecular mechanisms underlying observed associations. In the post-GWAS and big data era, many genetic loci, microbial species, and other risk factors have been linked to various phenotypes. However, the translation of these findings into personalized medicine remains limited. I see promising opportunities in two areas. First, recent advances in artificial intelligence (AI) are facilitating genome annotation, risk prediction, and drug target discovery. Second, microfluidic organ-on-a-chip technologies, combined with the differentiation and culturing of human induced pluripotent stem cells (hiPSCs), enable the construction of individualized organ-on-a-chip systems for studying disease mechanisms and testing drugs, all while accounting for a person's unique genetic background.</p><p>My scientific journey has three important turning points. I received my bachelor's degree in biochemistry and switched to the field of bioinformatics for my master's. This was the first turning point that enabled me to establish my knowledge in both molecular biology and bioinformatics. The second turning point was when I successfully completed my Ph.D. project in systems genetics using a plant model organism in 2007. At the time, the first draft sequence of the human genome was just published, and genome-wide association studies (GWAS) began to emerge for genome-wide genetic screening. I saw an opportunity to extend my expertise from plant genomics to human genetics. This chance permitted me to cross the disciplinary border toward the field of medicine. The third turning point took place in 2013 when I further extended my research area from human genetics to the human gut microbiome. The first microbiome study was published in <i>Circulation Research</i> in 2015<sup>[</sup><span><sup>1</sup></span><sup>],</sup> which was highlighted in the <i>TIME</i> book “TIME 100 New Health Discoveries: How the latest breakthroughs affect your health and wellness”.<sup>[</sup><span><sup>2</sup></span><sup>]</sup> Then in 2016, our first metagenome-based study was published in <i>Science</i>, which was also highlighted on the cover.<sup>[</sup><span><sup>3</sup></span><sup>]</sup> These two studies marked the beginning of my scientific journey in the microbiome field. Recently, our studies revealed inter-individual differences in the gut microbiome and the underlying environmental and genetic factors<sup>[</sup><span><sup>4, 5</sup></span><sup>]</sup>, reported its temporal dynamics and stability,<sup>[</sup><span><sup>6, 7</sup></span><sup>]</sup> its strain-level genetic variants, as well as its interaction with genetics and diet in metabolic regulation.<sup>[</sup><span><sup>8</sup></span><sup>]</sup> Therefore, looking back my scientific journey, my diverse research background demonstrates the importance of stepping out of one's comfort zone by engaging in cross-disciplinary work.</p><p>Many individuals have shaped my journey. I am especially grateful to my postdoctoral supervisor, Prof. Cisca Wijmenga—a visionary scientist whose leadership and creativity have had a profound influence on my development. She initiated pioneering research lines in genetics, microbiome, and organ-on-a-chip technologies at the University Medical Center Groningen. These fields, once perceived as emerging or high-risk, have now become integral pillars of biomedical research and are central to major initiatives in precision medicine and systems biology.</p><p>Under her mentorship, I learned not only to think big and across disciplines but also to build bridges between fundamental science and translational applications. Her ability to identify promising directions ahead of time taught me the value of scientific courage, strategic vision, and collaborative leadership.</p><p>I often ask myself the same question, and there is probably no perfect answer. The pressure in academia is considerable, and the situation in China is even more severe than in the Netherlands.</p><p>I recently attended a TEDx talk by Kika Buhrmann, CEO of Nespresso Netherlands. She said that work is part of life, and that it's not about time management—after all, we all have the same amount of time. Instead, it's about energy management: how to manage your activities so that they give you energy rather than drain it. This reflects my approach as well. For example, it is important for me to take breaks of at least 1–2 h a day and longer ones after a period of intense work to recharge. I also keep a priority list—daily, weekly, and monthly— to help track progress and stay focused. And most importantly, I enjoy traveling, which helps me find balance and inspiration.</p><p>Science today is increasingly cross-disciplinary. My advice to early-career researchers and students is to stay curious, be bold, and embrace the unknown. Don't be afraid to step outside your comfort zone and think outside the box—this is often where the most exciting discoveries occur.</p><p>I strongly believe in TEAM science. Collaboration is extremely important, and working together across disciplines not only accelerates scientific progress but also enriches your own perspective. I am delighted to be able to work with a group of researchers at the Groningen Microbiome Hub who share a similar mission but with complementary expertise. For example, combining genetics with organ-on-a-chip technologies enables functional validation of disease mechanisms in a human-relevant context. Likewise, AI-driven models are transforming how we predict genetic risk, interpret non-coding variants, and discover drug targets. Such cross-pollination of ideas is accelerating the transition from data-rich to insight-rich science.</p><p>This recognition by the Royal Netherlands Academy of Arts and Sciences and the Royal Holland Society of Sciences and Humanities are deeply meaningful to me, and much of the credit goes to my team, colleagues, and collaborators. I am also grateful for the support from the University Medical Center Groningen, the University of Groningen, and the Lifelines Biobank—this achievement would not have been possible without them.</p><p>I feel that genetics-based journals underwent rapid growth in the past 20 years, along with the development of the genetics and genomics research fields. However, the field of genetics is currently encountering a bottleneck in the transition from association studies to translational research. I think “<i>Advanced Genetics</i>” should focus on the term “Advanced”: building a platform for cutting-edge and innovative breakthroughs. To better serve researchers and practitioners, I believe the journal should continue to evolve in several ways. First, they can promote more open and transparent science by supporting preprints, data sharing, and reproducible research practices. Second, they can actively encourage cross-disciplinary submissions that reflect the complexity of modern research. Third, journals can play a stronger role in mentoring the next generation of scientists by inviting them to join the Youth editorial board and offering them opportunities to bring their vision on future research to the field.</p><p>This article was edited by Yuming Hu, Wiley.</p><p>The author declares no conflict of interest.</p>","PeriodicalId":72071,"journal":{"name":"Advanced genetics (Hoboken, N.J.)","volume":"6 2","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ggn2.202500039","citationCount":"0","resultStr":"{\"title\":\"Advanced Dialogues: From Genomes to Microbiomes—A Cross-Disciplinary Journey\",\"authors\":\"Jingyuan Fu\",\"doi\":\"10.1002/ggn2.202500039\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>My research group, Integrative Omics in Systems Medicine, is affiliated at the University Medical Center Groningen, the Netherlands. Our research aims to understand host-microbe interactions in complex traits and diseases, for which we integrate genetics, microbiome, and large-scale omics data to identify risk factors and their interactions underlying inter-individual variation in disease susceptibility.</p><p>The most pressing challenges lie in the undefined causality and molecular mechanisms underlying observed associations. In the post-GWAS and big data era, many genetic loci, microbial species, and other risk factors have been linked to various phenotypes. However, the translation of these findings into personalized medicine remains limited. I see promising opportunities in two areas. First, recent advances in artificial intelligence (AI) are facilitating genome annotation, risk prediction, and drug target discovery. Second, microfluidic organ-on-a-chip technologies, combined with the differentiation and culturing of human induced pluripotent stem cells (hiPSCs), enable the construction of individualized organ-on-a-chip systems for studying disease mechanisms and testing drugs, all while accounting for a person's unique genetic background.</p><p>My scientific journey has three important turning points. I received my bachelor's degree in biochemistry and switched to the field of bioinformatics for my master's. This was the first turning point that enabled me to establish my knowledge in both molecular biology and bioinformatics. The second turning point was when I successfully completed my Ph.D. project in systems genetics using a plant model organism in 2007. At the time, the first draft sequence of the human genome was just published, and genome-wide association studies (GWAS) began to emerge for genome-wide genetic screening. I saw an opportunity to extend my expertise from plant genomics to human genetics. This chance permitted me to cross the disciplinary border toward the field of medicine. The third turning point took place in 2013 when I further extended my research area from human genetics to the human gut microbiome. The first microbiome study was published in <i>Circulation Research</i> in 2015<sup>[</sup><span><sup>1</sup></span><sup>],</sup> which was highlighted in the <i>TIME</i> book “TIME 100 New Health Discoveries: How the latest breakthroughs affect your health and wellness”.<sup>[</sup><span><sup>2</sup></span><sup>]</sup> Then in 2016, our first metagenome-based study was published in <i>Science</i>, which was also highlighted on the cover.<sup>[</sup><span><sup>3</sup></span><sup>]</sup> These two studies marked the beginning of my scientific journey in the microbiome field. Recently, our studies revealed inter-individual differences in the gut microbiome and the underlying environmental and genetic factors<sup>[</sup><span><sup>4, 5</sup></span><sup>]</sup>, reported its temporal dynamics and stability,<sup>[</sup><span><sup>6, 7</sup></span><sup>]</sup> its strain-level genetic variants, as well as its interaction with genetics and diet in metabolic regulation.<sup>[</sup><span><sup>8</sup></span><sup>]</sup> Therefore, looking back my scientific journey, my diverse research background demonstrates the importance of stepping out of one's comfort zone by engaging in cross-disciplinary work.</p><p>Many individuals have shaped my journey. I am especially grateful to my postdoctoral supervisor, Prof. Cisca Wijmenga—a visionary scientist whose leadership and creativity have had a profound influence on my development. She initiated pioneering research lines in genetics, microbiome, and organ-on-a-chip technologies at the University Medical Center Groningen. These fields, once perceived as emerging or high-risk, have now become integral pillars of biomedical research and are central to major initiatives in precision medicine and systems biology.</p><p>Under her mentorship, I learned not only to think big and across disciplines but also to build bridges between fundamental science and translational applications. Her ability to identify promising directions ahead of time taught me the value of scientific courage, strategic vision, and collaborative leadership.</p><p>I often ask myself the same question, and there is probably no perfect answer. The pressure in academia is considerable, and the situation in China is even more severe than in the Netherlands.</p><p>I recently attended a TEDx talk by Kika Buhrmann, CEO of Nespresso Netherlands. She said that work is part of life, and that it's not about time management—after all, we all have the same amount of time. Instead, it's about energy management: how to manage your activities so that they give you energy rather than drain it. This reflects my approach as well. For example, it is important for me to take breaks of at least 1–2 h a day and longer ones after a period of intense work to recharge. I also keep a priority list—daily, weekly, and monthly— to help track progress and stay focused. And most importantly, I enjoy traveling, which helps me find balance and inspiration.</p><p>Science today is increasingly cross-disciplinary. My advice to early-career researchers and students is to stay curious, be bold, and embrace the unknown. Don't be afraid to step outside your comfort zone and think outside the box—this is often where the most exciting discoveries occur.</p><p>I strongly believe in TEAM science. Collaboration is extremely important, and working together across disciplines not only accelerates scientific progress but also enriches your own perspective. I am delighted to be able to work with a group of researchers at the Groningen Microbiome Hub who share a similar mission but with complementary expertise. For example, combining genetics with organ-on-a-chip technologies enables functional validation of disease mechanisms in a human-relevant context. Likewise, AI-driven models are transforming how we predict genetic risk, interpret non-coding variants, and discover drug targets. Such cross-pollination of ideas is accelerating the transition from data-rich to insight-rich science.</p><p>This recognition by the Royal Netherlands Academy of Arts and Sciences and the Royal Holland Society of Sciences and Humanities are deeply meaningful to me, and much of the credit goes to my team, colleagues, and collaborators. I am also grateful for the support from the University Medical Center Groningen, the University of Groningen, and the Lifelines Biobank—this achievement would not have been possible without them.</p><p>I feel that genetics-based journals underwent rapid growth in the past 20 years, along with the development of the genetics and genomics research fields. However, the field of genetics is currently encountering a bottleneck in the transition from association studies to translational research. I think “<i>Advanced Genetics</i>” should focus on the term “Advanced”: building a platform for cutting-edge and innovative breakthroughs. To better serve researchers and practitioners, I believe the journal should continue to evolve in several ways. First, they can promote more open and transparent science by supporting preprints, data sharing, and reproducible research practices. Second, they can actively encourage cross-disciplinary submissions that reflect the complexity of modern research. 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引用次数: 0
摘要
我的研究小组,系统医学综合组学,隶属于荷兰格罗宁根大学医学中心。我们的研究旨在了解宿主-微生物在复杂性状和疾病中的相互作用,为此我们整合了遗传学,微生物组学和大规模组学数据,以确定疾病易感性个体间差异的危险因素及其相互作用。最紧迫的挑战在于未定义的因果关系和观察到的关联背后的分子机制。在后gwas和大数据时代,许多基因位点、微生物物种和其他危险因素与各种表型相关。然而,将这些发现转化为个性化医疗仍然有限。我在两个领域看到了有希望的机会。首先,人工智能(AI)的最新进展正在促进基因组注释、风险预测和药物靶点发现。其次,微流控器官芯片技术与人类诱导多能干细胞(hipsc)的分化和培养相结合,能够构建个性化的器官芯片系统,用于研究疾病机制和测试药物,同时考虑到个人独特的遗传背景。我的科学之旅有三个重要的转折点。我获得了生物化学学士学位,然后转到生物信息学领域攻读硕士学位。这是第一个转折点,使我在分子生物学和生物信息学方面建立了自己的知识。第二个转折点是2007年,我成功地完成了系统遗传学博士项目,使用了一种植物模式生物。当时,人类基因组序列初稿刚刚公布,全基因组关联研究(genome-wide association studies, GWAS)开始出现,用于全基因组遗传筛选。我看到了一个机会,可以将我的专业知识从植物基因组学扩展到人类遗传学。这个机会使我能够跨越学科界限,进入医学领域。第三个转折点发生在2013年,我进一步将我的研究领域从人类遗传学扩展到人类肠道微生物组。第一项微生物组研究于2015年发表在《循环研究》杂志上,并在《时代》杂志的《时代100项新的健康发现:最新的突破如何影响你的健康》一书中得到了强调然后在2016年,我们的第一个基于宏基因组的研究发表在《科学》杂志上,这也是封面上的重点这两项研究标志着我在微生物学领域的科学之旅的开始。最近,我们的研究揭示了肠道微生物组的个体间差异及其潜在的环境和遗传因素[4,5],报道了其时间动态和稳定性[6,7],其菌株水平的遗传变异,以及其在代谢调节中与遗传和饮食的相互作用因此,回顾我的科学之旅,我多样化的研究背景证明了走出自己的舒适区,从事跨学科工作的重要性。很多人影响了我的人生。我特别感谢我的博士后导师Cisca wijmenga教授,他是一位有远见的科学家,他的领导能力和创造力对我的发展产生了深远的影响。她在格罗宁根大学医学中心发起了遗传学、微生物组和器官芯片技术的开创性研究。这些领域曾经被视为新兴或高风险领域,现在已成为生物医学研究的不可或缺的支柱,是精准医学和系统生物学重大举措的核心。在她的指导下,我不仅学会了从宏观和跨学科的角度思考,还学会了在基础科学和转化应用之间架起桥梁。她能够提前发现有前途的方向,这让我明白了科学勇气、战略眼光和协作领导力的价值。我经常问自己同样的问题,可能没有完美的答案。学术界的压力是相当大的,中国的情况甚至比荷兰更严重。我最近参加了荷兰奈斯派索公司首席执行官Kika Buhrmann的TEDx演讲。她说,工作是生活的一部分,与时间管理无关——毕竟,我们都有同样多的时间。相反,它是关于能量管理:如何管理你的活动,让它们给你能量,而不是消耗它。这也反映了我的做法。例如,对我来说,每天至少休息1-2小时,在一段时间的紧张工作后休息更长时间来充电是很重要的。我也有一个优先级列表——每天、每周、每月——以帮助跟踪进度并保持专注。最重要的是,我喜欢旅行,这有助于我找到平衡和灵感。今天的科学越来越多地是跨学科的。我对初入职场的研究人员和学生们的建议是:保持好奇,大胆,拥抱未知。 不要害怕走出你的舒适区,跳出框框去思考——这往往是最令人兴奋的发现发生的地方。我坚信团队科学。合作是极其重要的,跨学科的合作不仅能加速科学进步,还能丰富你自己的观点。我很高兴能够与格罗宁根微生物中心的一组研究人员合作,他们有着相似的使命,但具有互补的专业知识。例如,将遗传学与器官芯片技术相结合,可以在与人类相关的背景下对疾病机制进行功能验证。同样,人工智能驱动的模型正在改变我们预测遗传风险、解释非编码变异和发现药物靶点的方式。这种思想的交叉融合正在加速从数据丰富的科学向洞察力丰富的科学的转变。荷兰皇家艺术与科学院和荷兰皇家科学与人文学会的认可对我来说意义深远,这在很大程度上要归功于我的团队、同事和合作者。我还要感谢格罗宁根大学医学中心、格罗宁根大学和生命线生物银行的支持——没有他们,就不可能有今天的成就。我觉得在过去的20年里,随着遗传学和基因组学研究领域的发展,以遗传学为基础的期刊经历了快速的增长。然而,遗传学领域目前在从关联研究向转化研究过渡的过程中遇到了瓶颈。我认为“先进遗传学”应该着眼于“先进”这个词:搭建一个前沿创新突破的平台。为了更好地为研究人员和从业者服务,我认为杂志应该在几个方面继续发展。首先,它们可以通过支持预印本、数据共享和可复制的研究实践来促进更加开放和透明的科学。其次,他们可以积极鼓励反映现代研究复杂性的跨学科提交。第三,期刊可以在指导下一代科学家方面发挥更大的作用,邀请他们加入青年编辑委员会,并为他们提供机会,将他们对未来研究的看法带到该领域。本文由Wiley胡玉明编辑。作者声明不存在利益冲突。
Advanced Dialogues: From Genomes to Microbiomes—A Cross-Disciplinary Journey
My research group, Integrative Omics in Systems Medicine, is affiliated at the University Medical Center Groningen, the Netherlands. Our research aims to understand host-microbe interactions in complex traits and diseases, for which we integrate genetics, microbiome, and large-scale omics data to identify risk factors and their interactions underlying inter-individual variation in disease susceptibility.
The most pressing challenges lie in the undefined causality and molecular mechanisms underlying observed associations. In the post-GWAS and big data era, many genetic loci, microbial species, and other risk factors have been linked to various phenotypes. However, the translation of these findings into personalized medicine remains limited. I see promising opportunities in two areas. First, recent advances in artificial intelligence (AI) are facilitating genome annotation, risk prediction, and drug target discovery. Second, microfluidic organ-on-a-chip technologies, combined with the differentiation and culturing of human induced pluripotent stem cells (hiPSCs), enable the construction of individualized organ-on-a-chip systems for studying disease mechanisms and testing drugs, all while accounting for a person's unique genetic background.
My scientific journey has three important turning points. I received my bachelor's degree in biochemistry and switched to the field of bioinformatics for my master's. This was the first turning point that enabled me to establish my knowledge in both molecular biology and bioinformatics. The second turning point was when I successfully completed my Ph.D. project in systems genetics using a plant model organism in 2007. At the time, the first draft sequence of the human genome was just published, and genome-wide association studies (GWAS) began to emerge for genome-wide genetic screening. I saw an opportunity to extend my expertise from plant genomics to human genetics. This chance permitted me to cross the disciplinary border toward the field of medicine. The third turning point took place in 2013 when I further extended my research area from human genetics to the human gut microbiome. The first microbiome study was published in Circulation Research in 2015[1], which was highlighted in the TIME book “TIME 100 New Health Discoveries: How the latest breakthroughs affect your health and wellness”.[2] Then in 2016, our first metagenome-based study was published in Science, which was also highlighted on the cover.[3] These two studies marked the beginning of my scientific journey in the microbiome field. Recently, our studies revealed inter-individual differences in the gut microbiome and the underlying environmental and genetic factors[4, 5], reported its temporal dynamics and stability,[6, 7] its strain-level genetic variants, as well as its interaction with genetics and diet in metabolic regulation.[8] Therefore, looking back my scientific journey, my diverse research background demonstrates the importance of stepping out of one's comfort zone by engaging in cross-disciplinary work.
Many individuals have shaped my journey. I am especially grateful to my postdoctoral supervisor, Prof. Cisca Wijmenga—a visionary scientist whose leadership and creativity have had a profound influence on my development. She initiated pioneering research lines in genetics, microbiome, and organ-on-a-chip technologies at the University Medical Center Groningen. These fields, once perceived as emerging or high-risk, have now become integral pillars of biomedical research and are central to major initiatives in precision medicine and systems biology.
Under her mentorship, I learned not only to think big and across disciplines but also to build bridges between fundamental science and translational applications. Her ability to identify promising directions ahead of time taught me the value of scientific courage, strategic vision, and collaborative leadership.
I often ask myself the same question, and there is probably no perfect answer. The pressure in academia is considerable, and the situation in China is even more severe than in the Netherlands.
I recently attended a TEDx talk by Kika Buhrmann, CEO of Nespresso Netherlands. She said that work is part of life, and that it's not about time management—after all, we all have the same amount of time. Instead, it's about energy management: how to manage your activities so that they give you energy rather than drain it. This reflects my approach as well. For example, it is important for me to take breaks of at least 1–2 h a day and longer ones after a period of intense work to recharge. I also keep a priority list—daily, weekly, and monthly— to help track progress and stay focused. And most importantly, I enjoy traveling, which helps me find balance and inspiration.
Science today is increasingly cross-disciplinary. My advice to early-career researchers and students is to stay curious, be bold, and embrace the unknown. Don't be afraid to step outside your comfort zone and think outside the box—this is often where the most exciting discoveries occur.
I strongly believe in TEAM science. Collaboration is extremely important, and working together across disciplines not only accelerates scientific progress but also enriches your own perspective. I am delighted to be able to work with a group of researchers at the Groningen Microbiome Hub who share a similar mission but with complementary expertise. For example, combining genetics with organ-on-a-chip technologies enables functional validation of disease mechanisms in a human-relevant context. Likewise, AI-driven models are transforming how we predict genetic risk, interpret non-coding variants, and discover drug targets. Such cross-pollination of ideas is accelerating the transition from data-rich to insight-rich science.
This recognition by the Royal Netherlands Academy of Arts and Sciences and the Royal Holland Society of Sciences and Humanities are deeply meaningful to me, and much of the credit goes to my team, colleagues, and collaborators. I am also grateful for the support from the University Medical Center Groningen, the University of Groningen, and the Lifelines Biobank—this achievement would not have been possible without them.
I feel that genetics-based journals underwent rapid growth in the past 20 years, along with the development of the genetics and genomics research fields. However, the field of genetics is currently encountering a bottleneck in the transition from association studies to translational research. I think “Advanced Genetics” should focus on the term “Advanced”: building a platform for cutting-edge and innovative breakthroughs. To better serve researchers and practitioners, I believe the journal should continue to evolve in several ways. First, they can promote more open and transparent science by supporting preprints, data sharing, and reproducible research practices. Second, they can actively encourage cross-disciplinary submissions that reflect the complexity of modern research. Third, journals can play a stronger role in mentoring the next generation of scientists by inviting them to join the Youth editorial board and offering them opportunities to bring their vision on future research to the field.