Systems Biology,Systems Medicine,Systems Pharmacology: The What and The Why

Systems biology is today such a widespread discipline that it becomes difficult to propose a clear definition of what it really is. For some, it remains restricted to the genomic field. For many, it designates the integrated approach or the corpus of computational methods employed to handle the vast amount of biological or medical data and investigate the complexity of the living. Although defining systems biology might be difficult, on the other hand its purpose is clear: systems biology, with its emerging subfields systems medicine and systems pharmacology, clearly aims at making sense of complex observations/experimental and clinical datasets to improve our understanding of diseases and their treatments without putting aside the context in which they appear and develop. In this short review, we aim to specifically focus on these new subfields with the new theoretical tools and approaches that were developed in the context of cancer. Systems pharmacology and medicine now give hope for major improvements in cancer therapy, making personalized medicine closer to reality. As we will see, the current challenge is to be able to improve the clinical practice according to the paradigm shift of systems sciences.     

Systems Approaches to Biology and Disease Enable Translational Systems Medicine

The development and application of systems strategies to biology and disease are transforming medical research and clinical practice in an unprecedented rate.In the foreseeable future,clinicians,medical researchers,and ultimately the consumers and patients will be increasingly equipped with a deluge of personal health information,e.g.,whole genome sequences,molecular profiling of diseased tissues,and periodic multi-analyte blood testing of biomarker panels for disease and wellness.The convergence of these practices will enable accurate prediction of disease susceptibility and early diagnosis for actionable preventive schema and personalized treatment regimes tailored to each individual.It will also entail proactive participation from all major stakeholders in the health care system.We are at the dawn of predictive,preventive,personalized,and participatory(P4) medicine,the fully implementation of which requires marrying basic and clinical researches through advanced systems thinking and the employment of high-throughput technologies in genomics,proteomics,nanofluidics,single-cell analysis,and computation strategies in a highly-orchestrated discipline we termed translational systems medicine.     

Adaptive Capacity of Social-Ecological Systems: Lessons from Immune Systems

How do systems respond to disturbances? The capacity of a system to respond to disturbances varies for different types of disturbance regimes. We distinguish two types of responses: one that enables the system to absorb disturbances from an existing disturbance regime, and one that enables a system to reconstruct itself after a fundamental change in a disturbance regime. We use immune systems as a model for how systems can deal with disturbances, and use this model to derive insights in adaptive capacity of social-ecological systems. We identify a tension between the two types of responses where one benefits from learning and memory while the other requires fast-turnover of experience. We discuss how this may affect building up adaptive capacity of social-ecological systems.     

Biomesogenic Matrix Systems

Abstract

The bifunctionally reactive nucleoside and distant nucleoside analogs adenosine (Ado), S-[(adenine-9-yl)methoxyethyl]-L-cysteine (Na-salt) (cysA) and 9-vinyladenine (vA) in aqueous solutions assemble on complementary polyuridylic acid templates to form complex lyomesophases. The systems are investigated by polarizing microscopy, differential scanning calorimetry (DSC) and ¹H- and ³¹P-nmr spectroscopies, assisted by molecular modeling studies. The results indicate the importance of biomesogenic (pre)ordering in nucleic acid native and artificial matrix reactions.     

Nickel-based Enzyme Systems

Of the eight known nickel enzymes, all but glyoxylase I catalyze the use and/or production of gases central to the global carbon, nitrogen, and oxygen cycles. Nickel appears to have been selected for its plasticity in coordination and redox chemistry and is able to cycle through three redox states (1+, 2+, 3+) and to catalyze reactions spanning ∼1.5 V. This minireview focuses on the catalytic mechanisms of nickel enzymes, with an emphasis on the role(s) of the metal center. The metal centers vary from mononuclear to complex metal clusters and catalyze simple hydrolytic to multistep redox reactions.Seven of the eight known nickel enzymes (1). CODH² interconverts CO and CO₂; ACS utilizes CO; the nickel ARD produces CO; hydrogenase generates/utilizes hydrogen gas; MCR generates methane; urease produces ammonia; and SOD generates O₂.

TABLE 1

Nickel-containing enzymes

分枝杆菌分泌系统

分泌系统对于具有特殊细胞被膜结构的分枝杆菌,尤其是致病性分枝杆菌的存活和毒力非常重要.不少重要的致病因子或存活因子都通过特定的分泌系统进入环境,包括宿主体内.本文从分泌系统的基因、结构组成、分泌底物、转运机制及其与致病菌毒力的关系等几个方面介绍了分枝杆菌(mycobacteria)通用型分泌系统(general secretion pathway,SecA1)、替代型分泌系统(accessory Sec system,SecA2)、双精氨酸分泌系统(twin-arginine translocation,Tat)和Ⅶ型分泌系统(typeⅦsecretion systems,T7S system or ESX)4种分泌系统,并重点分析了Tat分泌系统.这些知识有利于从分泌系统及其底物的角度揭示结核分枝杆菌等胞内致病菌存活和逃避宿主免疫的机理,将为研发新的结核病控制措施提供依据.     

Systems chemical biology

The increasing availability of data related to genes, proteins and their modulation by small molecules has provided a vast amount of biological information leading to the emergence of systems biology and the broad use of simulation tools for data analysis. However, there is a critical need to develop cheminformatics tools that can integrate chemical knowledge with these biological databases and simulation approaches, with the goal of creating systems chemical biology.     

动物的婚配制度

婚配制度是动物种群个体为获得配偶普遍采取的一种行为策略。一般分为单配制、一雄多雌制、一雌多雄制和混交制。作为动物的一种进化稳定对策,婚配制度又具有一定的可塑性,有时可以逆转,有时又是兼性的。配偶外交配主要存在于单配制物种中特别是单配制鸟类中。其发现表明通过观察个体间联系来确定的“社会性婚配制度”和通过个体实际上的交配对象来描述的“遗传性婚配制度”有可能存在差异。婚配制度影响有害动物的不育控制,在存在繁殖性竞争的情况下,对单配制和一雄多雌制而言,不育效果最佳。     

Systems cell biology

Upon starvation, Grh1, a peripheral membrane protein located at endoplasmic reticulum (ER) exit sites and early Golgi in Saccharomyces cerevisiae under growth conditions, relocates to a compartment called compartment for unconventional protein secretion (CUPS). Here we report that CUPS lack Golgi enzymes, but contain the coat protein complex II (COPII) vesicle tethering protein Uso1 and the Golgi t-SNARE Sed5. Interestingly, CUPS biogenesis is independent of COPII- and COPI-mediated membrane transport. Pik1- and Sec7-mediated membrane export from the late Golgi is required for complete assembly of CUPS, and Vps34 is needed for their maintenance. CUPS formation is triggered by glucose, but not nitrogen starvation. Moreover, upon return to growth conditions, CUPS are absorbed into the ER, and not the vacuole. Altogether our findings indicate that CUPS are not specialized autophagosomes as suggested previously. We suggest that starvation triggers relocation of secretory and endosomal membranes, but not their enzymes, to generate CUPS to sort and secrete proteins that do not enter, or are not processed by enzymes of the ER–Golgi pathway of secretion.