2016 Neuroscience Prize
Born in mainland China in 1948, Mu-Ming Poo was raised in Taiwan, where his family moved when he was only a year old. His father was an aeronautical engineer and helped develop Poo’s early interest in physics, a subject he majored in at Tsinghua University in Taiwan. “Of course, in those days, kids interested in science almost always went into physics,” says Poo.
After graduation in 1970, Poo decided to continue his education in the United States, where his father had also been trained. Poo was accepted into the graduate physics program at Johns Hopkins University in Baltimore. While there, he took a course in physiology, and quickly realized that he wanted to focus on biophysics. “I was fascinated by the possibility of understanding physical principles underlying biology,” he recalls. Under the guidance of his thesis advisor, biophysicist Richard Cone, Poo began developing tools to measure protein mobility in cell membranes, research that led in 1974 to his first publication in a major medical journal, Nature. In this work, Poo developed a now-widely used biophysical method known as photobleaching recovery, which enables scientists to measure the diffusion rate of proteins in cells.
After receiving his PhD, Poo remained in the United States, first doing postdoctoral research at Purdue University and then, in 1976, becoming an assistant professor in the Department of Physiology and Biophysics at the University of California, Irvine, where he established his own laboratory. At these institutions, he developed a new technique—in situ electrophoresis—for manipulating the distribution of proteins in cell membranes. “During the first ten years of my research career, I was focusing on the problem of protein mobility and localization within cell membranes,” Poo recalls. “I wanted to know what makes proteins to become localized to the places in cells where they can perform their functions, against the randomizing effect of diffusion”
By the mid-1980s, Poo had become particularly interested in the localization of proteins at synapses, the junctions between neurons where the cells transmit their messages. “I thought how synaptic structure is formed is a very intriguing biological problem,” he says, “and to pursue this problem he moved his lab in 1985 to Yale University School of Medicine, which was starting a new section of molecular neurobiology. A few years later he accepted a professorship at Columbia University and then, in 1996, at the University of California, San Diego. Throughout this period, Poo worked on a variety of problems regarding the cell biology of synapse formation. One of these problems involved the extension of axon growth cones of motor neurons. (Growth cones are the tips of axons, a thread-like process of nerve cells that undergoes extensive growth to seek out the target cells and form synaptic connections with them), Using cultured embryonic nerve and muscle cells of the frog Xenopus laevis, Poo and his colleagues discovered that motor axon growth cones are able to secrete the neurotransmitter acetylcholine before coming in contact with muscle cells and that functional synapses can form rapidly — within minutes — after nerve-muscle contact. He also found that neurotrophins (proteins that promote the growth and survival of neurons) could quickly increase the effectiveness of neuromuscular junctions, a discovery that helped the development of a new field of study on the role of neurotrophins in synaptic plasticity and cognitive functions. In addition, Poo and his collaborators developed a way of measuring the effect of extracellular factors on the direction of axon growth within neurons. Known as the “growth cone turning assay,” this method is now widely used for assaying single-axon responses to many families of proteins known as axon guidance factors. Using this method, his laboratory found that the turning decision of an axon in response to any given guidance factor can switch between attraction and repulsion, depending on the internal state of the neuron, such as the level of cyclic nucleotides.
In 2000, Poo moved his lab to the Department of Molecular and Cell Biology at the University of California, Berkeley, where he served as Paul Licht Distinguished Profession in Biology. While at UC Berkeley, Poo began a series of studies on the mechanisms that determine the differentiation of axons and dendrites (the extensions of neurons that receive impulses from other cells) during early neuron development. The studies led to many discoveries, including the role of cyclic nucleotides and specific proteins in determining the axonal vs. dendritic fate, and the finding of a cytoskeletal “meshwork” at the axon initial segment (a specialized region of the axon where neuronal impulses initiate) that regulates the cellular transport of proteins into the developing axon. This research has significantly enhanced our understanding of the biological mechanisms that underlie neuronal polarization during cell development.
In the area of synaptic plasticity, Poo has made important contribution in understanding how neuronal activity (spiking) may induce long-term changes in the efficiency of synaptic transmission, which is essential for learning and memory. He has helped to characterize the phenomenon of spike-timing-dependent plasticity (STDP), a biological process that regulates the synaptic strength between neurons by the order of spiking of pre- and postsynaptic neurons. Poo and his colleagues demonstrated that STDP plays a critical role in the developmental refinement of connections between visual neurons and that STDP mechanisms may be used by the brain to store information on temporal sequence and time intervals between events. This research has led to a deeper understanding of activity-dependent synaptic plasticity and its role in neural circuit functions.
“I characterize my career as a random walk,” Poo says. “When I bump into an interesting problem, I work on it for as long as I can contribute. Then I move on.”
Poo has received numerous professional honors throughout his career, including memberships in the US National Academy of Sciences, the Chinese Academy of Sciences, Academia Sinica (Taiwan), and Hong Kong Academy of Science. In 1999, Poo helped found the Institute of Neuroscience (ION) at the Chinese Academy of Sciences in Shanghai. He has devoted much of the ensuing years to solidifying its reputation as an exceptional institution of neuroscience research. For more than a decade, Poo traveled back and forth every few weeks between Shanghai and Berkeley. “It finally became too much,” he says, ruefully. As a result, he has recently taken an emeritus position at UC Berkeley in order to concentrate his efforts in China.