抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Cell signaling by receptor-tyrosine kinases

BIOE 402. Medical Technology Assessment. 2 or 3 hours. Bioentrepreneur course. Assessment of medical technology in the context of commercialization. Objectives, competition, market share, funding, pricing, manufacturing, growth, and intellectual property; many issues unique to biomedical products. Course Information: 2 undergraduate hours. 3 graduate hours. Prerequisite(s): Junior standing or above and consent of the instructor.

“Bioinformatics” 특집을 내면서

The large-scale organization of metabolic networks

Metabolites are the end products of cellular regulatory processes, and their levels can be regarded as the ultimate response of biological systems to genetic or environmental changes. In parallel to the terms ‘transcriptome’ and ‘proteome’, the set of metabolites synthesized by a biological system constitute its ‘metabolome’. Yet, unlike other functional genomics approaches, the unbiased simultaneous identification and quantification of plant metabolomes has been largely neglected. Until recently, most analyses were restricted to profiling selected classes of compounds, or to fingerprinting metabolic changes without sufficient analytical resolution to determine metabolite levels and identities individually. As a prerequisite for metabolomic analysis, careful consideration of the methods employed for tissue extraction, sample preparation, data acquisition, and data mining must be taken. In this review, the differences among metabolite target analysis, metabolite profiling, and metabolic fingerprinting are clarified, and terms are defined. Current approaches are examined, and potential applications are summarized with a special emphasis on data mining and mathematical modelling of metabolism.

https://link.springer.com/content/pdf/10.1023%2FA%3A1013713905833.pdf

Metabolomics - the link between genotypes and phenotypes

The specificity of cellular responses to receptor stimulation is encoded by the spatial and temporal dynamics of downstream signalling networks. Temporal dynamics are coupled to spatial gradients of signalling activities, which guide pivotal intracellular processes and tightly regulate signal propagation across a cell. Computational models provide insights into the complex relationships between the stimuli and the cellular responses, and reveal the mechanisms that are responsible for signal amplification, noise reduction and generation of discontinuous bistable dynamics or oscillations.

/pdf/cell-signalling-dynamics-in-time-and-space-1kenz3nw5d.pdf

Cell-signalling dynamics in time and space

itogen-activated protein kinase (MAPK) cascades can operate as bistable switches residing in either of two different stable states MAPK cascades are often embedded in positive feedback loops, which are considered to be a prerequisite for bistable behavior Here we demonstrate that in the absence of any imposed feedback regulation, bistability and hysteresis can arise solely from a distributive kinetic mechanism of the two-site MAPK phosphorylation and dephosphorylation Importantly, the reported kinetic properties of the kinase (MEK) and phosphatase M (MKP3) of extracellular signal‐regulated kinase (ERK) fulfill the essential requirements for generating a bistable switch at a single MAPK cascade level Likewise, a cycle where multisite phosphorylations are performed by different kinases, but dephosphorylation reactions are catalyzed by the same phosphatase, can also exhibit bistability and hysteresis Hence, bistability induced by multisite covalent modification may be a widespread mechanism of the control of protein activity

/pdf/signaling-switches-and-bistability-arising-from-multisite-57ru0i15d1.pdf

Signaling switches and bistability arising from multisite phosphorylation in protein kinase cascades

Functional organization of signal transduction into protein phosphorylation cascades, such as the mitogen-activated protein kinase (MAPK) cascades, greatly enhances the sensitivity of cellular targets to external stimuli The sensitivity increases multiplicatively with the number of cascade levels, so that a tiny change in a stimulus results in a large change in the response, the phenomenon referred to as ultrasensitivity In a variety of cell types, the MAPK cascades are imbedded in long feedback loops, positive or negative, depending on whether the terminal kinase stimulates or inhibits the activation of the initial level Here we demonstrate that a negative feedback loop combined with intrinsic ultrasensitivity of the MAPK cascade can bring about sustained oscillations in MAPK phosphorylation Based on recent kinetic data on the MAPK cascades, we predict that the period of oscillations can range from minutes to hours The phosphorylation level can vary between the base level and almost 100% of the total protein The oscillations of the phosphorylation cascades and slow protein diffusion in the cytoplasm can lead to intracellular waves of phospho-proteins

Negative feedback and ultrasensitivity can bring about oscillations in the mitogen-activated protein kinase cascades.

http://epbi-radivot.cwru.edu/EPBI473/files/wk10SBMLtools/egfrKholodenkoJBC99.pdf

Quantification of Short Term Signaling by the Epidermal Growth Factor Receptor

The discovery of molecular signalling machines such as Ras nanoclusters, spatial activity gradients and flexible network circuitries involving transcriptional feedback, are beginning to reveal the design principles of spatiotemporal organization that are crucial for signalling network function and cell fate decisions.

/pdf/signalling-ballet-in-space-and-time-45guym84oj.pdf

Boris N. Kholodenko

Papers

Cell-signalling dynamics in time and space

Signaling switches and bistability arising from multisite phosphorylation in protein kinase cascades

Negative feedback and ultrasensitivity can bring about oscillations in the mitogen-activated protein kinase cascades.

Quantification of Short Term Signaling by the Epidermal Growth Factor Receptor

Signalling ballet in space and time