Welcome to Louis!

Louis is visiting us for three months as a summer student. A very warm welcome to him!

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Welcome to Daniel and Alexey!

Daniel and Alexey are our two new PhD students who started recently. A very warm welcome to both of them!


Estevez Prado_Daniel Alexey Morgunov

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Use of Host-like Peptide Motifs in Viral Proteins Is a Prevalent Strategy in Host-Virus Interactions

Viruses interact extensively with host proteins, but the mechanisms controlling these interactions are not well understood. We present a comprehensive analysis of eukaryotic linear motifs (ELMs) in 2,208 viral genomes and reveal that viruses exploit molecular mimicry of host-like ELMs to possibly assist in host-virus interactions. Using a statistical genomics approach, we identify a large number of potentially functional ELMs and observe that the occurrence of ELMs is often evolutionarily conserved but not uniform across virus families. Some viral proteins contain multiple types of ELMs, in striking similarity to complex regulatory modules in host proteins, suggesting that ELMs may act combinatorially to assist viral replication. Furthermore, a simple evolutionary model suggests that the inherent structural simplicity of ELMs often enables them to tolerate mutations and evolve quickly. Our findings suggest that ELMs may allow fast rewiring of host-virus interactions, which likely assists rapid viral evolution and adaptation to diverse environments. The paper can be found here.

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Controlling entropy to tune the functions of intrinsically disordered regions

Intrinsically disordered regions (IDRs) are fundamental units of protein function and regulation. Despite their inability to form a unique stable tertiary structure in isolation, many IDRs adopt a defined conformation upon binding and achieve their function through their interactions with other biomolecules. However, this requirement for IDR functionality seems to be at odds with the high entropic cost they must incur upon binding an interaction partner. How is this seeming paradox resolved? While increasing the enthalpy of binding is one approach to compensate for this entropic cost, growing evidence suggests that inherent features of IDRs, for instance repeating linear motifs, minimise the entropic cost of binding. Moreover, this control of entropic cost can be carefully modulated by a range of regulatory mechanisms, such as alternative splicing and post-translational modifications, which enable allosteric communication and rheostat-like tuning of IDR function. In that sense, the high entropic cost of IDR binding can be advantageous by providing tunability to protein function. In addition to biological regulatory mechanisms, modulation of entropy can also be controlled by environmental factors, such as changes in temperature, redox-potential and pH. These principles are extensively exploited by a number of organisms, including pathogens. They can also be utilised in bioengineering, synthetic biology and in pharmaceutical applications such as increasing bioavailability of protein therapeutics. The review by Tilman Flock, Robert J Weatheritt, Natasha S Latysheva and M Madan Babu can be found here.

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Classification of Intrinsically Disordered Regions and Proteins

The review by Robin van der Lee et al can be found here.

 

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Structural polymorphism in the N-terminal oligomerization domain of NPM1

Nucleophosmin (NPM1) is a multifunctional phospho-protein with critical roles in ribosome biogenesis, tumor suppression, and nucleolar stress response. Here we show that the N-terminal oligomerization domain of NPM1 (Npm-N) exhibits structural polymorphism by populating conformational states ranging from a highly ordered, folded pentamer to a highly disordered monomer. The monomer–pentamer equilibrium is modulated by posttranslational modification and protein binding. Phosphorylation drives the equilibrium in favor of monomeric forms, and this effect can be reversed by Npm-N binding to its interaction partners. We have identified a short, arginine-rich linear motif in NPM1 binding partners that mediates Npm-N oligomerization. We propose that the diverse functional repertoire associated with NPM1 is controlled through a regulated unfolding mechanism signaled through posttranslational modifications and intermolecular interactions. The paper with Marija Buljan et al can be found here.

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Guilhem Chalancon’s talk at UKSG 2014 is on Youtube

Channelling information flows: a young researcher’s approach to knowledge management

https://www.youtube.com/watch?v=ST7I1Wq3epM

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AJ Venkatakrishnan talks about what it’s like to be a PhD student with the MRC

https://www.youtube.com/watch?v=ApIvIr6gqI4

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Melis Kayikci is our group’s Scientific Manager

Many congratulations to Dr. Melis Kayikci, who has been officially promoted to become our group’s Scientific Manager from the 1st of April 2014! Melis will now oversee various scientific administrative responsibilities in our group in addition to providing scientific support with computing and research.


Melis Kayikci

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Guilhem Chalancon will be giving an oral presentation at the PLS conference in Paris!

Guilhem is going to be a speaker at the PLS Conference in Paris which is held between 26-28 May 2014. His title “PLS Path Modelling of the molecular origins of gene expression noise” has been accepted for oral presentation.

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