生物成像和基因技术的快速发展，给生命科学带来了革命性的变化。自2010年北京大学生物动态光学成像中心（2018年更名为北京大学生物医学前沿创新中心，BIOPIC）成立以来，跨学科科学家们致力于发展前沿生物技术，并利用这些技术去解决生物学的基础问题和威胁人民健康的医学问题。中心的研究成果提高了人们对生物系统、传染性疾病和非传染性疾病的认识。
其创始人、单分子生物学领域先驱谢晓亮回顾了中心的发展历程，并分享了他关于单细胞技术发展的愿景：
是什么原因促使您成立BIOPIC？
我的学术生涯以生物物理化学家起步，因为我喜欢操作仪器。物理化学为理解生物分子过程提供了工具，推动实现了许多生命科学研究的进步。最初，我专注于生物成像，使用单分子荧光显微镜和其他工具，监测、分析和操纵活细胞中单分子的活动。这些工具改变了生物问题的研究方式：科学家们可以在不破坏生命体正常生理状态的情况下研究单个分子的活动。
随着下一代测序技术的发展，科学家们能够以更快的速度、更低的成本完成基因组分析。这场生物科学领域的技术革命，带来了精准医学的新时代。看到新型测序技术的应用潜力，我开始转向单细胞基因组学，并开发了属于团队自己的测序仪。同时，我萌生了建立一个中心，专门研究基础科学和开发医学前沿技术的想法。我和另外两位北大校友——苏晓东教授和黄岩谊教授向母校提出了这个想法，于是2010年，BIOPIC正式成立。
BIOPIC为何与众不同？
BIOPIC是一个技术驱动的生物医学研究中心，集基础研究、技术研发和临床应用于一体。我认为研究工具的突破和跨学科的整合对推动生命科学研究的发展至关重要。为此，BIOPIC引进了拥有多学科背景的研究人员，包括我这样的物理化学学家或生物物理学家，还有结构生物学家、分子生物学家，以及从事生物技术或工程、数学，和计算科学的研究人员。中心的很多突破性的生物技术都是跨学科合作的成果。我认为，BIOPIC的跨学科水平是数一数二的。
强调临床转化也是BIOPIC的独特之处。BIOPIC虽有很多科研成果发表在顶级学术期刊上，但这不是中心师生的最终目标。BIOPIC鼓励研究人员进行技术产业化，与临床医生合作，将技术应用至临床转化。BIOPIC的科学家们有志于推动基础科学的发展，也期望运用我们的技术造福社会。
BIOPIC关注的前沿技术有哪些？
最初，基于我早年间在哈佛大学的单分子成像工作，BIOPIC被命名为生物动态光学成像中心。如今中心的研究范围大为拓展。BIOPIC专注于单细胞基因组学技术，包括高通量测序、基因编辑和微流控。在大数据分析的加持下，这些技术加上单分子成像、超分辨率和无标记成像技术，可以用于推进基础科学研究——从基因组学、遗传学和分子生物学，到发育生物学、肿瘤免疫学和生物信息学。BIOPIC也重视技术的临床转化。BIOPIC开发的全基因组扩增技术可以实现高覆盖率的测序，并已用于胚胎植入前基因筛选。BIOPIC师生们研发的纠错码测序、基于CRISPR的测序，以及一种安全、高效的基因编辑工具，已经用于分析人类胚胎发育、干细胞和肿瘤微环境，为生殖医学、癌症和传染病的诊疗提供参考。
您为什么聚焦单细胞基因组学？
单分子技术使科学家们能够在分子水平上解释生命过程，这是20世纪的一项重要进展。单细胞基因组学是一种下一代测序技术，有可能带来一场更大的革命。我相信，其影响比人类基因组计划更大。它能帮助科学家们探究细胞内存在的全部DNA和RNA，绘制基因组结构和功能图谱，回答DNA或RNA携带的遗传信息如何控制细胞功能等问题。这将提供对于一些基础生命科学问题的新认知，并为临床应用带来新的可能性，包括产前基因检测和癌症诊断等。
要想在这个快速发展的领域站稳脚跟，中国必须发展单细胞基因组学技术，包括研发知识产权完全属于自己的测序仪。而BIOPIC正在推动这样的技术发展。
单细胞技术如何为精准医学铺路？
精准医学必须考虑到基因的个体差异性。单细胞基因组学能够加深医生对疾病的遗传学理解，确定最适合个体的治疗方法。例如在癌症治疗方面，利用下一代测序技术，医生可以分析单个肿瘤细胞及其微环境，确定新的治疗靶标。最近，BIOPIC的科学家利用单细胞RNA测序技术揭示了肝癌中单个免疫细胞的动态，为开发潜在的治疗策略带来了启示。
此外，BIOPIC的研究团队与北京大学第三医院的乔杰院长合作，提高了胚胎植入前的基因诊断和筛查水平。基于早期开发的单细胞全基因组扩增技术，BIOPIC研发的新方法已被用于从已知患有单基因遗传病的夫妇中，高精度地选择健康胚胎。
BIOPIC如何促进研究转化？
BIOPIC的目标是将技术转化为应用。转化研究需要一个健康流畅的生态系统，北京大学在各个基础领域都有丰富的资源和优势。临床上，北大有附属医院；地理位置上，北大离中关村科技园区的生物中心也足够近，这里有生物技术巨头（如百济神州），也有许多初创企业。BIOPIC的研究人员们已经创办了6家生物技术公司，其中有5家是在北京注册的。BIOPIC为科学家们提供足够的支持和发展空间，让他们敢想敢做，同时也扶持了一个关系紧密的校内-校外共同体，让科学家之间的协同作用激发出各种奇思妙想，并转化为临床成果，服务于整个社会。
您对BIOPIC的期望是什么？
我们的目标是BIOPIC成为生物医学领域世界领先的研究机构，推动前沿生物技术的原创性研究，开发和利用创新的生物成像与基因技术，为在分子和细胞水平上探索基础生命科学和医学研究等问题提供工具。我也期望BIOPIC的工作能够转化为技术和医学上的突破，最终造福社会和全人类。
The rapid development of biological imaging and gene technology has brought revolutionary changes to life science. Since the establishment of the Center for Biodynamic Optical Imaging at Peking University in 2010 (renamed As Peking University Biomedical Frontier Innovation Center in 2018), interdisciplinary scientists have been committed to developing cutting-edge biotechnology and using these technologies to solve fundamental problems in biology and medical problems that threaten people's health. The centre's research results have raised awareness of biological systems, communicable and non-communicable diseases.
Its founder, Xie Xiaoliang, a pioneer in the field of single molecular biology, reviewed the development of the Center and shared his vision for the development of single cell technology:
What prompted you to set up BIOPIC?
I started my academic career as a biophysical chemist because I enjoyed operating instruments. Physical chemistry provides tools for understanding biomolecular processes and has driven many advances in life science research. Initially, I focused on biological imaging, using single-molecule fluorescence microscopy and other tools to monitor, analyze and manipulate the activity of single molecules in living cells. These tools have transformed the way biological problems are studied: scientists can study the activity of individual molecules without disrupting the normal physiology of living organisms.
With the development of next-generation sequencing technology, scientists are able to complete genome analysis faster and at lower cost. This technological revolution in the field of biological science has brought about a new era of precision medicine. Seeing the potential of new sequencing technologies, I turned to single-cell genomics and developed the team's own sequencer. At the same time, I had the idea of establishing a center specializing in basic science and developing cutting-edge technologies in medicine. I and two other PKU alumni, Prof. Su Xiaodong and Prof. Huang Yanyi, proposed the idea to our Alma mater, and BIOPIC was officially established in 2010.
Why is BIOPIC different?
BIOPIC is a technology-driven biomedical research center that integrates basic research, technology development and clinical applications. I believe that breakthroughs in research tools and cross-disciplinary integration are critical to advancing life science research. To do this, BIOPIC brings in researchers with multidisciplinary backgrounds, including physical chemists or biophysicists like myself, as well as structural biologists, molecular biologists, and researchers working in biotechnology or engineering, mathematics, and computational sciences. Many of the breakthrough biotechnologies at the center are the result of interdisciplinary collaborations. I think BIOPIC is one of the best interdisciplinary companies in the world.
The emphasis on clinical transformation is also unique to BIOPIC. BIOPIC has many scientific research achievements published in top academic journals, but this is not the ultimate goal of the center's teachers and students. BIOPIC encourages researchers to industrialize their technologies and work with clinicians to transform them into clinical applications. BIOPIC scientists are interested in advancing basic science and also looking to use our technology for the benefit of society.
What cutting-edge technologies are BIOPIC focused on?
Originally, BIOPIC was named the Center for Biodynamic Optical Imaging based on my earlier single-molecule imaging work at Harvard University. Now the centre's research has expanded considerably. BIOPIC focuses on single-cell genomics technologies, including high-throughput sequencing, gene editing and microfluidics. Powered by big data analytics, these technologies, along with single-molecule imaging, super-resolution and unlabeled imaging, can be used to advance basic scientific research -- from genomics, genetics and molecular biology, to developmental biology, tumor immunology and bioinformatics. BIOPIC also focuses on clinical transformation of technology. BIOPIC's genome-wide amplification technology enables sequencing with high coverage and has been used for pre-implantation gene screening in embryos. BIOPIC's error-correcting sequencing, CRISPR-based sequencing, and a safe and efficient gene editing tool have been used to analyze human embryo development, stem cells and tumor microenvironment for reproductive medicine, cancer and infectious disease diagnosis and treatment.
Why are you focusing on single-cell genomics?
Single molecule technology enabled scientists to explain life processes at the molecular level, an important advance of the 20th century. Single-cell genomics is a next-generation sequencing technology that has the potential to revolutionize things even more. I believe the impact is bigger than the human Genome Project. It can help scientists explore all the DNA and RNA in a cell, map the structure and function of the genome, and answer questions such as how the genetic information carried by DNA or RNA controls cell function. This will provide new insights into fundamental life science issues and open up new possibilities for clinical applications, including prenatal genetic testing and cancer diagnosis.
To gain a foothold in this fast-growing field, China will have to develop single-cell genomics technology, including sequencing machines with proprietary intellectual property. And BIOPIC is driving just that.
How can single-cell technology pave the way for precision medicine?
Precision medicine must take into account individual differences in genes. Single-cell genomics can deepen doctors' understanding of the genetics of diseases and determine the best treatments for individuals. In cancer treatment, for example, using next-generation sequencing technology, doctors can analyze individual tumor cells and their microenvironment to identify new therapeutic targets. Recently, BIOPIC scientists have used single-cell RNA sequencing technology to reveal the dynamics of individual immune cells in liver cancer, shedding light on the development of potential treatment strategies.
In addition, BIOPIC's research team collaborated with Qiao Jie, president of Peking University Third Hospital, to improve genetic diagnosis and screening of embryos before implantation. Based on an earlier single-cell genome-wide amplification technique developed by BIOPIC, the new method has been used to select healthy embryos with high accuracy from couples known to have single-gene genetic disorders.
How does BIOPIC facilitate research transformation?
BIOPIC's goal is to translate the technology into applications. Translational research needs a healthy and smooth ecosystem, and Peking University has abundant resources and advantages in various basic fields. Clinically, PKU has affiliated hospitals; The university is also geographically close enough to the biohub of the Zhongguancun Science park, home to biotech giants such as Baekje Shenzhou, as well as many start-ups. Researchers at BIOPIC have founded six biotechnology companies, five of which are registered in Beijing. BIOPIC provides enough support and development space for scientists to dare to think and do, but also supports a close relationship between the university and the university community, so that the synergy between scientists to inspire a variety of ideas, and translate into clinical results, to serve the whole society.
What are your expectations for BIOPIC?
Our goal is to become the world's leading research institution in biomedicine, to promote original research in cutting-edge biotechnology, to develop and utilize innovative bioimaging and genetic technologies, and to provide tools for exploring fundamental life science and medical research issues at the molecular and cellular levels. I also expect BIOPIC's work to translate into technological and medical breakthroughs that will ultimately benefit society and humanity.