A Bioorthogonal Small‐Molecule‐Switch System for Controlling Protein Function in Live Cells

Liu, Peng; Calderon, Abram; Konstantinidis, Georgios; Hou, Jian; Voss, Stephanie; Chen, Xi; Li, Fu; Banerjee, Soumya; Hoffmann, Jan‐Erik; Theiss, Christiane; Dehmelt, Leif; Wu, Yao‐Wen

doi:10.1002/ange.201403463

Cited by 11 publications

(2 citation statements)

References 42 publications

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“…This would enable us to couple within host models of viral kinetics to models of how viruses spread between hosts, enabling modelling of diseases at multiple scales. Our work also suggests a generality and power of dynamical models in capturing rich features of diverse complex systems ranging from immune systems and intra-cellular regulatory networks to global scientific collaboration networks [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34].…”

Section: Discussionmentioning

confidence: 99%

A Computational Technique to Estimate Within-Host Productively Infected Cell Lifetimes in Emerging Viral Infections

Banerjee¹

2017

Interdiscip. Descr. Complex Syst.

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Emerging viruses cause a lot of fatalities as they jump to humans from other species. Here we develop a novel technique to computationally estimate an important parameter of within-host viral infection: the lifespan of infected cells. Our approach is general and can be applied to a large class of viruses and leverages experimental data from replicon studies. Current techniques have difficulties reliably estimating infected cell lifetimes due to parameter identifiability and correlation of parameters. The infected cell lifetime is an important parameter that gives an estimate of how fast virus levels will decline. Our method would also help determine if some infected cells are short-lived or have longer lifespans with the consequence that longer lived cells could be reservoirs of infection. This would give a mechanistic understanding of why particular cell types are reservoirs of infection and may motivate therapy targeted towards these cell types. We apply our technique to West Nile virus (WNV), an emerging disease of public health relevance related to Zika virus. Our analysis suggests that the most abundant infectible cells are short-lived and could motivate therapy that targets these particular cells. Our approach is very general and can be combined with more traditional methods of using differential equation models to simulate viremia in hosts: the combination of these two techniques will likely yield results that may not be achievable using the models in isolation. This will be of great interest especially in modelling emerging diseases.

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Section: Discussionmentioning

confidence: 99%

A Computational Technique to Estimate Within-Host Productively Infected Cell Lifetimes in Emerging Viral Infections

Banerjee¹

2017

Interdiscip. Descr. Complex Syst.

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“…The current work highlights the significance of simple mathematical and dynamical models that reveal insights into biological processes as has been done previously in immunology and cell biology [4][5][6][7][8][9][10][11][12][13].…”

Section: Discussionmentioning

confidence: 99%

Optimal Strategies for Virus Propagation

Soumya¹

2016

Adv Robot Autom

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Abstract. This paper explores a number of questions regarding optimal strategies evolved by viruses upon entry into a vertebrate host. The infected cell life cycle consists of a non-productively infected stage in which it is producing virions but not releasing them and of a productively infected stage in which it is just releasing virions. The study explores why the infected cell cycle should be so delineated, something which is akin to a classic "bang-bang control" or all-or-none principle. The times spent in each of these stages represent a viral strategy to optimize peak viral load. Increasing the time spent in the non-productively infected phase (τ 1 ) would lead to a concomitant increase in peak viremia. However increasing this time would also invite a more vigorous response from Cytotoxic T-Lymphocytes (CTLs). Simultaneously, if there is a vigorous antibody response, then we might expect τ 1 to be high, in order that the virus builds up its population and conversely if there is a weak antibody response, τ 1 might be small. These tradeoffs are explored using a mathematical model of virus propagation using Ordinary Differential Equations (ODEs). The study raises questions about whether common viruses have actually settled into an optimum, the role for reliability and whether experimental infections of hosts with non-endemic strains could help elicit answers about viral progression.

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“Molecular Activity Painting”: schaltbare, lichtgesteuerte Manipulation in lebenden Zellen

et al. 2017

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Die akute subzelluläre Rekrutierung von Proteinen ist eine leistungsfähige Methode zur Untersuchung biologischer Netzwerke. Hoch‐dynamische Signalprozesse an der Plasmamembran können bisher jedoch nur bedingt räumlich und zeitlich untersucht werden. Insbesondere durch laterale Diffusion an der Plasmamembran ist eine anhaltende lokale Steuerung molekularer Funktionen schwer zu realisieren. Hier wird die “Molekulare‐Aktivitäts‐Malerei” (Molecular Activity Painting, MAP) vorgestellt, eine neuartige Technik, die photoaktivierbare chemisch induzierte Dimerisierung (pCID) mit immobilisierten künstlichen Rezeptoren kombiniert. Die Immobilisierung der künstlichen Rezeptoren durch oberflächengebundene Antikörper hemmt die laterale Diffusion. Hierdurch wird schnelles und stabiles Malen (Painting) von Signalmolekülen und deren Aktivität an der Plasmamembran im Mikrometermaßstab ermöglicht. Stabiles Malen des RhoA‐Myosin‐Aktivators GEF‐H1 kann kontraktile Actomyosin‐Strukturen in lebenden Zellen induzieren.

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A Bioorthogonal Small‐Molecule‐Switch System for Controlling Protein Function in Live Cells

Cited by 11 publications

References 42 publications

A Computational Technique to Estimate Within-Host Productively Infected Cell Lifetimes in Emerging Viral Infections

A Computational Technique to Estimate Within-Host Productively Infected Cell Lifetimes in Emerging Viral Infections

Optimal Strategies for Virus Propagation

“Molecular Activity Painting”: schaltbare, lichtgesteuerte Manipulation in lebenden Zellen

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