A decade after the foundation of the Institute of Neuroscience in Shanghai, the field enjoys rapid growth and can attract young investigators back from abroad. Michael Gross reports. A decade after the foundation of the Institute of Neuroscience in Shanghai, the field enjoys rapid growth and can attract young investigators back from abroad. Michael Gross reports. In a country that can look back on five millennia of cultural history, people like to take the long view. Thus, Mu-Ming Poo, the director of the Institute of Neuroscience (ION) of the Chinese Academy of Sciences (CAS) at Shanghai, celebrated the recent tenth anniversary of his institute by recalling early 20th century pioneers of Chinese science such as De-Pei Feng, who founded a neurophysiology laboratory at Peking Union Medical College in 1934, and Hsiang-Tong Zhang, who set up a lab in Shanghai in 1957 (N.B. all Chinese names in this article are written with the given name first). With all the respect he pays to these early pioneers, however, Poo has to admit that “it was not until [the] 1980s that stable support for basic scientific research became available, and only in the past decade that quality rather than quantity of publications began to be considered a merit.” The Chinese Society for Neuroscience was founded in 1995. Then came the rapid expansion phase fuelled by economic growth: science funding in China increased steeply in the first decade of the new century, with annual increases typically around 20% (although the 2011 figure is more modest at 12.5%). Thus the ION, founded in 1999, arrived very much at the right time to serve as the flagship of a rapidly growing research community, which is now widely recognised by observers both inside and outside the country. In the last few years, many young investigators trained in the US or Europe have returned to China to start their own groups. One of them is Fang Fang (see Q & A on pages R444–R446 of this issue), who obtained a PhD from the University of Minnesota in 2007 and now leads a group at Peking University investigating visual perception using both psychophysical and imaging methods. Peking (or Beijing) University, based in the 20-million megalopolis capital Beijing, one of the top universities in the country, has very much the size and structure of a Western university, with around 12,000 undergraduates, a similar number of master's students, and over 7,000 doctoral students. The subject canon is also similar to universities in the US, says Fang, with the exception that psychology is less prominent. Fang receives research funding from the two major funding agencies, namely the National Natural Science Foundation of China (NSFC) (http://www.nsfc.gov.cn) and the Ministry of Science and Technology (MOST) (http://www.most.gov.cn). “The decisions are made based on peer-reviewing, similar to the funding agencies in western countries (e.g. NSF and NIH in the USA),” says Fang, who is also involved in peer-reviewing applications from other researchers. “Although some improvements are needed, I think the system is moving ahead in a right direction,” Fang concludes. In 2010, 23 percent of applications made to the NSFC found support. Improvements may be needed in the funding mechanisms for large centres and infrastructure projects, such as MRI laboratories. There has been repeated criticism that these large grants are based on personal favours rather than on scientific merit. In an editorial published in Science last September, for instance, Yigong Shi and Yi Rao criticize that the application guidelines for large grants specify “national needs”, which, the authors claim, are clearly designed with certain intended recipients in mind. “To obtain major grants in China, it is an open secret that doing good research is not as important as schmoozing with powerful bureaucrats and their favourite experts,” Shi and Rao conclude. Nevertheless, substantial amounts of good research have already emerged from China in the last decade and have found international recognition. Asked to cite one breakthrough paper from the last five years, Fang picks one from Current Biology (Xiao et al., (2008) 18, 1922–1926). In this work, Fang explains, “Cong Yu at Beijing Normal University and his collaborators created a ‘double training’ technique to enable perceptual learning [improvement of feature discrimination and object recognition by training] to completely transfer to untrained retinal locations. This paper seriously challenged the very fundamental assumption that perceptual learning is specific to the trained retinal location, and therefore the various theories of perceptual learning that are constrained by this specificity.” Xu Zhang from the ION in Shanghai reviewed pain research in China for the special issue of Science China – Life Sciences published on the occasion of the institute's 10th birthday. He reports that “pain research is a well established field of research in China, due to the long history of pain treatments in clinics and hospitals and the pain therapy known as acupuncture analgesia”. Remarkably, as Zhang relates, research into the mechanisms underlying the ancient methods of acupuncture remained active during the Cultural Revolution, giving the field a head start afterwards. Apart from this, much effort is invested in studying chronic or neuropathic pain, which doesn't have an obvious physiological cause and remains poorly understood. Apart from the centres in Beijing and Shanghai, the laboratories of Yun-Quing Li and San-Jue Hu at the Fourth Military Medical University in Xi'an have made significant contributions to the molecular analysis of chronic pain. Researchers are also gaining a more detailed picture of the molecular mechanisms of the transmission of pain. Zhang's group at the ION has recently discovered a new regulatory system involving the protein Follistatin-like-1 (Neuron (2011) 69, 974–987). “Follistatin-like 1 (FSTL1) is the first endogenous activator of a sodium pump that has been identified in the body, and regulates the synaptic transmission and nociceptive responses,” Zhang explains. “Reduction in FSTL1 in sensory afferents contributes to a mechanism of chronic pain (Cell Research (2011) 21, 697–699). Moreover, so far, this is an important neuromodulator and novel neurotransmission mechanism identified first in China.” Researchers in China are now also hoping to address the processing of pain in the brain and the pathways producing the emotional impact it has. While much research has studied the pain processing at the periphery and in the spinal cord, the effects in the brain still remain to be explored. Hong Kong: a special situation“As Special Administrative Region in China, Hong Kong runs its own science policy and support system,” explains Benjamin Peng, a professor at the Hong Kong University of Science and Technology (HKUST). As in mainland China, the neuroscience community in Hong Kong has grown considerably during the last decade, Peng says. In addition to the local meetings of the Hong Kong Society of Neurosciences, Hong Kong has also hosted many international neuroscience-related meetings in recent years, notably the Gordon Research Conference on Molecular and Cellular Neurobiology, which is held there every other year. Local neuroscientists from the University of Hong Kong, Chinese University, HKUST, Baptist University and Polytechnic University, have also contributed to educating international students, including postgraduates and junior faculty members from all Asian countries, Australia, India and Iran.“Neuroscience research in Hong Kong is mainly supported by the Research Grants Council (RGC) through a peer-reviewed, investigator-initiated General Research Fund scheme,” Peng explains. “However, Hong Kong currently spends less than 1% of its GDP in research, much lower than China's 2.2%. This large discrepancy will undoubtedly erode Hong Kong's competitiveness in research infrastructure and manpower. Despite the relative shortage in research funding, Hong Kong neuroscientists have made significant inroads in gaining world-wide recognition in both basic and clinical neuroscience. Throughout its history, Hong Kong has projected to the world as a cosmopolitan city with cultural confluence, progressive outlook and well-developed infrastructure. Neuroscience in Hong Kong, although still in fledgling state, can flourish in this region if more generous support is provided,” he concludes. “As Special Administrative Region in China, Hong Kong runs its own science policy and support system,” explains Benjamin Peng, a professor at the Hong Kong University of Science and Technology (HKUST). As in mainland China, the neuroscience community in Hong Kong has grown considerably during the last decade, Peng says. In addition to the local meetings of the Hong Kong Society of Neurosciences, Hong Kong has also hosted many international neuroscience-related meetings in recent years, notably the Gordon Research Conference on Molecular and Cellular Neurobiology, which is held there every other year. Local neuroscientists from the University of Hong Kong, Chinese University, HKUST, Baptist University and Polytechnic University, have also contributed to educating international students, including postgraduates and junior faculty members from all Asian countries, Australia, India and Iran. “Neuroscience research in Hong Kong is mainly supported by the Research Grants Council (RGC) through a peer-reviewed, investigator-initiated General Research Fund scheme,” Peng explains. “However, Hong Kong currently spends less than 1% of its GDP in research, much lower than China's 2.2%. This large discrepancy will undoubtedly erode Hong Kong's competitiveness in research infrastructure and manpower. Despite the relative shortage in research funding, Hong Kong neuroscientists have made significant inroads in gaining world-wide recognition in both basic and clinical neuroscience. Throughout its history, Hong Kong has projected to the world as a cosmopolitan city with cultural confluence, progressive outlook and well-developed infrastructure. Neuroscience in Hong Kong, although still in fledgling state, can flourish in this region if more generous support is provided,” he concludes. The extremely rapid population expansion in China throughout most of the 20th century, which was then slowed significantly by the one-child policy introduced in 1978, means that there is now a fast-growing population of older citizens. Predictably, this leads to higher incidence of age-related diseases, including neurodegenerative diseases such as Alzheimer's and Parkinson's disease, which could soon become a significant economic burden to the less numerous generations born during the one-child policy. Thus, neurodegenerative disease is also a focus of neuroscience research in China, with research being conducted at numerous centres including Huazhong University of Science and Technology in Wuhan, at the University of Science and Technology of China in Hefei and at the Central South University in Changsha, as well as in the big centres in Hong Kong, Shanghai and Beijing. At the Hong Kong University of Science and Technology (HKUST), Nancy Ip leads a team studying a range of topics, including neurodegenerative diseases and neuromuscular disorders. In her most recent work, Ip's team discovered a new role for a cell-surface protein called EphA4 in the regulation of brain plasticity. They found that EphA4-mediated signalling can control unrestrained activity in the brain by regulating the level of neurotransmitter receptors. As many neurodegenerative diseases are associated with impaired neurotransmission in the brain, these insights suggest that EphA4 may be a suitable target for developing novel treatments for cognitive deficits in patients with such diseases. Earlier this year, Ip was also appointed as Dean of Science and Director of the State Key Laboratory of Molecular Neuroscience at HKUST. Ip said, “Our recent breakthroughs in molecular neuroscience are very exciting as they bring us one step closer towards developing effective therapies for neurodegenerative diseases and disorders, many of which are age-related. The global population is rapidly aging and, unless novel therapeutic drugs are developed soon, we will face a potential healthcare crisis. Through our recently established State Key Laboratory of Molecular Neuroscience, we are committed to undertake leading-edge research and push current research boundaries to address this critical need.” Ip's institute maintains a close partnership with the ION at Shanghai, with joint annual retreats and research collaborations. However, science funding in Hong Kong remains largely separate from mainland China (see box). Over in mainland China, Sarah Perrett is a group leader at the CAS Institute of Biophysics (IBP) in Beijing. During her time as a research fellow in protein folding at Cambridge University, she went on a study visit to the IBP in 1998, funded by the Royal Society. She then spent a year studying Chinese full-time and returned to the IBP with a Royal Society post-doctoral fellowship. She now holds a full professorship there, which is essentially a permanent position, although she still has to apply for visas on a regular basis. With her team of ten (three permanent post-doctoral staff members and up to two new PhD students each year), Perrett investigates the molecular mechanism of amyloid formation by prion proteins and other misfolding events relevant to neurodegenerative disease. Their most recent paper, investigating the connection between the propensity to propagate a prion state and the rates of individual molecular steps of amyloid fibril assembly, was featured on the cover of JBC (J. Biol. Chem. (2011) 286, 12101–12107). Like her Chinese colleagues, Perrett receives funding through competitive grants from the Chinese funding agencies, MOST, NSFC, and CAS. Here, her intensive language studies are proving valuable, as all grants to these agencies must still be submitted in Chinese. Foreign collaborations have also been funded by western agencies, including the Royal Society, but in these cases the funding is paid out to her foreign collaborators. A decade after what must have appeared as a very brave move at the time, Perrett is still enthusiastic about the opportunities she enjoys in Beijing. “It's an exciting time for science in China!” she says. “The fact that there has been a huge reverse-brain-drain in the last few years, and the comparative funding situation in China compared to the West, means that there is some really ambitious and exciting science going on here that most Western institutions would struggle to support,” Perrett concludes. One of the first western organisations to establish scientific contacts was Germany's Max Planck Society (MPG), which already sent a delegation to China in 1974, and has maintained lively exchange programs ever since. “The Max Planck Institutes that work in the field of neurosciences usually have doctoral students and post-docs from the leading universities in China and from the CAS institutes,” says Barbara Spielmann from the society. In 2005, MPG and CAS set up the Partner Institute of Computational Biology in Shanghai, with a truly international staff, including directors both from China and from Germany. In 2009–2010, Germany and China held a joint bilateral year of science and education, involving over 150 events in both countries and culminating in a final celebration at the Expo 2010 at Shanghai. Nearly 50 German universities held ‘Chinese weeks’ in the summer of 2010. Nikos Logothetis, director of the department ‘Physiology of Cognitive Processes’ at the Max Planck Institute for Biological Cybernetics in Tübingen, has visited Chinese neuroscience laboratories on several occasions. “It's very, very impressive what they try to do, and how fanatically they support science. Really amazing!” he enthuses. He also praises the international spirit in China's neuroscience community: “They are strongly welcoming interactions with other nations; in fact they try to get as many of them as possible for scientific advisory boards, for guest professorships and so on.” All in all, as both Chinese and foreign researchers are finding the prospect of working in China increasingly attractive, it looks like China is claiming its place among the leading research nations. This appears to be true for neuroscience as much as for other fields, e.g. genomics. After decades of severe brain-drain, it looks as though the drain can be stopped. “I think the brain-drain has been diminished significantly, at least in biology,” says Fang Fang. “With the development of economy and the improvement of scientific evaluation systems in China, the brain-drain can be stopped.” Fang also points to a 2008 government plan, the Recruitment Program of Global Experts (also called the one-thousand talents plan), which aims to recruit established scientists working in well-known research universities and institutes. Modern institutes, like the Kavli Institute at Peking University and the McGovern Institutes of Brain Research soon to be established at Peking University and Tsinghua University, are actively recruiting non-Chinese scientists. “I expect some non-Chinese world-class scientists will take PI positions in these institutes,” says Fang. Sarah Perrett agrees: “Science in China is gradually becoming more internationalized. At the moment, the majority of scientists in China are of Chinese origin, but that is already changing.”