It has been a dream that theoretical biology can be extensively applied in experimental biology to accelerate the understanding of the sophiscated movements in living organisms. A brave assay and an excellent example ...It has been a dream that theoretical biology can be extensively applied in experimental biology to accelerate the understanding of the sophiscated movements in living organisms. A brave assay and an excellent example were represented by enzymology, in which the well-established physico-chemistry is used to describe, to fit, to predict and to improve enzyme reactions. Before the modern bioinformatics, the developments of the combination of theoretical biology and experimental biology have been mainly limited to various classic formulations. The systematic use of graphic rules by Prof. Kuo-Chen Chou and his co-workers has significantly facilitated to deal with complicated enzyme systems. With the recent fast progress of bioinformatics, prediction of protein structures and various protein attributes have been well established by Chou and co-workers, stimulating the experimental biology. For example, their recent method for predicting protein subcellular localization (one of the important attributes of proteins) has been extensively applied by scientific colleagues, yielding many new results with thousands of citations. The research by Prof. Chou is characterized by introducing novel physical concepts as well as powerful and elegant mathematical methods into important biomedical problems, a focus throughout his career, even when facing enormous difficulties. His efforts in 50 years have greatly helped us to realize the dream to make “theoretical and experimental biology in one”. Prof. Richard Giege is well known for his multi-disciplinary research combining physics, chemistry, enzymology and molecular biology. His major focus of study is on the identity of tRNAs and their interactions with aminoacyl-tRNA synthetases (aaRS), which are of critical importance to the fidelity of protein biosynthesis. He and his colleagues have carried out the first crystallization of a tRNA/aaRS complex, that between tRNAAsp and AspRS from yeast. The determination of the complex structure contributed significantly to under- stand the展开更多
Theory allows studying why Evolution might select core genetic commitment circuit topologies over alternatives. The nonlinear dynamics of the underlying gene regulation together with the unescapable subtle interplay o...Theory allows studying why Evolution might select core genetic commitment circuit topologies over alternatives. The nonlinear dynamics of the underlying gene regulation together with the unescapable subtle interplay of intrinsic biochemical noise impact the range of possible evolutionary choices. The question of why certain genetic regulation circuits might present robustness to phenotype-delivery breaking over others, is therefore of high interest. Here, the behavior of systematically more complex commitment circuits is studied, in the presence of intrinsic noise, with a focus on two aspects relevant to biology： parameter asymmetry and time-scale separation. We show that phenotype delivery is broken in simple two- and three-gene circuits. In the two-gene circuit, we show how stochastic potential wells of different depths break commitment. In the three-gene circuit, we show that the onset of oscillations breaks the commitment phenotype in a systematic way. Finally, we also show that higher dimensional circuits （four-gene and five-gene circuits） may be intrinsically more robust.展开更多
Stochastic dynamics pervades gene regulation. Despite being random, the dynamics displays a kind of innate structure. In fact, two stochastic forces combine driving efforts： one force originates from the gradient of ...Stochastic dynamics pervades gene regulation. Despite being random, the dynamics displays a kind of innate structure. In fact, two stochastic forces combine driving efforts： one force originates from the gradient of the underlying stochastic potential, and the other originates from the mathematical curl of the probability flux. The curl force gives rise to rotation. The gradient force gives rise to drift. Together they give rise to helical behavior. Here, it is shown that around and about the vicinity of attractive fixed points, the gradient force naturally wanes but the curl force is found to remain high. This leads to a locally noticeably different type of stochastic track near and about attractive fixed points, compared to tracks in regions where drift dominates. The consistency of this observation with the experimental fact that, in biology, fate commitment appears to not be a-priory locked-in, but rather necessitating active maintenance, is discussed. Hence attractive fixed-points are not only fuzzy, but may effectively be, locally, ＂more free＂.展开更多
Mitochondria (singular, mitochondrion) are important organelles that in the center of energy production and information processing. They are primarily known as the powerhouse of the cell, as they produce most of the e...Mitochondria (singular, mitochondrion) are important organelles that in the center of energy production and information processing. They are primarily known as the powerhouse of the cell, as they produce most of the energy that cells need for all kinds of activities.This is done by generating the cellular energy currency,adenosine triphosphate (ATP). In addition to energy production, mitochondria play a central role in regulating signal transduction as signaling organelles.Mitochondria control Ca2+ homeostasis, reactive oxygen species (ROS) generation and elimination, cellular differentiation, and programmed cell death (apoptosis).They are involved in many signaling pathways including calcium, mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K)-Akt,mammalian target of rapamycin (mTOR), wingless-int (Wnt), Ras, and insulin signaling pathways.展开更多
Cancer immunotherapy has now been conclusively shown to be capable of producing durable responses for a substantial number of patients.Adoptive cell transfer and checkpoint blockade therapies in particular both demons...Cancer immunotherapy has now been conclusively shown to be capable of producing durable responses for a substantial number of patients.Adoptive cell transfer and checkpoint blockade therapies in particular both demonstrate that antigen-specific immune responses can be dramatically effective,even in previously refractory late stage disease.Such developments,together with advances in technology,have strongly encouraged revisiting the concept of neoantigen vaccines.Here we introduce basic ideas in the field to allow investigators from diverse backgrounds to understand these developments,grasp current issues,and contribute to further progress.展开更多
文摘It has been a dream that theoretical biology can be extensively applied in experimental biology to accelerate the understanding of the sophiscated movements in living organisms. A brave assay and an excellent example were represented by enzymology, in which the well-established physico-chemistry is used to describe, to fit, to predict and to improve enzyme reactions. Before the modern bioinformatics, the developments of the combination of theoretical biology and experimental biology have been mainly limited to various classic formulations. The systematic use of graphic rules by Prof. Kuo-Chen Chou and his co-workers has significantly facilitated to deal with complicated enzyme systems. With the recent fast progress of bioinformatics, prediction of protein structures and various protein attributes have been well established by Chou and co-workers, stimulating the experimental biology. For example, their recent method for predicting protein subcellular localization (one of the important attributes of proteins) has been extensively applied by scientific colleagues, yielding many new results with thousands of citations. The research by Prof. Chou is characterized by introducing novel physical concepts as well as powerful and elegant mathematical methods into important biomedical problems, a focus throughout his career, even when facing enormous difficulties. His efforts in 50 years have greatly helped us to realize the dream to make “theoretical and experimental biology in one”. Prof. Richard Giege is well known for his multi-disciplinary research combining physics, chemistry, enzymology and molecular biology. His major focus of study is on the identity of tRNAs and their interactions with aminoacyl-tRNA synthetases (aaRS), which are of critical importance to the fidelity of protein biosynthesis. He and his colleagues have carried out the first crystallization of a tRNA/aaRS complex, that between tRNAAsp and AspRS from yeast. The determination of the complex structure contributed significantly to under- stand the
文摘Theory allows studying why Evolution might select core genetic commitment circuit topologies over alternatives. The nonlinear dynamics of the underlying gene regulation together with the unescapable subtle interplay of intrinsic biochemical noise impact the range of possible evolutionary choices. The question of why certain genetic regulation circuits might present robustness to phenotype-delivery breaking over others, is therefore of high interest. Here, the behavior of systematically more complex commitment circuits is studied, in the presence of intrinsic noise, with a focus on two aspects relevant to biology： parameter asymmetry and time-scale separation. We show that phenotype delivery is broken in simple two- and three-gene circuits. In the two-gene circuit, we show how stochastic potential wells of different depths break commitment. In the three-gene circuit, we show that the onset of oscillations breaks the commitment phenotype in a systematic way. Finally, we also show that higher dimensional circuits （four-gene and five-gene circuits） may be intrinsically more robust.
文摘Stochastic dynamics pervades gene regulation. Despite being random, the dynamics displays a kind of innate structure. In fact, two stochastic forces combine driving efforts： one force originates from the gradient of the underlying stochastic potential, and the other originates from the mathematical curl of the probability flux. The curl force gives rise to rotation. The gradient force gives rise to drift. Together they give rise to helical behavior. Here, it is shown that around and about the vicinity of attractive fixed points, the gradient force naturally wanes but the curl force is found to remain high. This leads to a locally noticeably different type of stochastic track near and about attractive fixed points, compared to tracks in regions where drift dominates. The consistency of this observation with the experimental fact that, in biology, fate commitment appears to not be a-priory locked-in, but rather necessitating active maintenance, is discussed. Hence attractive fixed-points are not only fuzzy, but may effectively be, locally, ＂more free＂.
文摘Mitochondria (singular, mitochondrion) are important organelles that in the center of energy production and information processing. They are primarily known as the powerhouse of the cell, as they produce most of the energy that cells need for all kinds of activities.This is done by generating the cellular energy currency,adenosine triphosphate (ATP). In addition to energy production, mitochondria play a central role in regulating signal transduction as signaling organelles.Mitochondria control Ca2+ homeostasis, reactive oxygen species (ROS) generation and elimination, cellular differentiation, and programmed cell death (apoptosis).They are involved in many signaling pathways including calcium, mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K)-Akt,mammalian target of rapamycin (mTOR), wingless-int (Wnt), Ras, and insulin signaling pathways.
基金This work was supported by a National Basic Research Program of China(973 Program,No.2014CB745202)the Shenzhen Peacock Team Project(No.KQTD2015033117210153)+1 种基金the Shenzhen Science and Technology Innovation Committee Basic Science Research Grants(No.JCYJ20170413154523577,No.JCYJ20150629151046896)the Guangdong Natural Science Funds for Distinguished Young Scholar Grant(No.S2013050016987).
文摘Cancer immunotherapy has now been conclusively shown to be capable of producing durable responses for a substantial number of patients.Adoptive cell transfer and checkpoint blockade therapies in particular both demonstrate that antigen-specific immune responses can be dramatically effective,even in previously refractory late stage disease.Such developments,together with advances in technology,have strongly encouraged revisiting the concept of neoantigen vaccines.Here we introduce basic ideas in the field to allow investigators from diverse backgrounds to understand these developments,grasp current issues,and contribute to further progress.
