Recent Research Highlights

2008 December
GeneSilico metaserver tops the CASP8 ranking in protein disorder prediction

The GeneSilico human predictors' group and several servers developed in the Bujnicki laboratory achieved high positions in rankings of the 8th Community-Wide Experiment on the Critical Assessment of Techniques for Protein Structure Prediction (CASP8), organized by the Protein Structure Prediction Center.

Servers for protein structure prediction and model quality assessment achieved respectable positions in their respective categories. The most successful was the GeneSilico metaserver for protein disorder prediction, which ranked as number 1 in its category. These successful servers are freely available to all academic researchers via the GeneSilico toolkit.


2008 October
Characterization of ubiquitin-associated (UBA) domain in inhibitor of apoptosis (IAP) proteins.

Janusz Bujnicki contributed a structural model to a collaborative study (led by Pascal Meier from the Breakthrough Toby Robins Breast Cancer Research Centre in London) that has characterized an evolutionarily conserved ubiquitin-associated (UBA) domain in inhibitor of apoptosis (IAP) proteins. An article entitled "IAPs contain an evolutionarily conserved ubiquitin-binding domain that regulates NF-kappaB as well as cell survival and oncogenesis" has been published in Nature Cell Biology and describes the following findings: UBA domain enables IAPs to bind to Lys 63-linked polyubiquitin and is essential for the oncogenic potential of cIAP1, to maintain endothelial cell survival and to protect cells from TNF-alpha-induced apoptosis. Moreover, the UBA domain is required for XIAP and cIAP2-MALT1 to activate NF-kappaB. The UBA domain of cIAP2-MALT1 stimulates NF-kappaB signalling by binding to polyubiquitylated NEMO. This publication identified IAPs as ubiquitin-binding proteins that contribute to ubiquitin-mediated cell survival, NF-kappaB signalling and oncogenesis.


2008 August
New rRNA modification enzymes discovered and characterized

Researchers from the Bujnicki laboratory predicted (with bioinformatics) and then experimentally confirmed that two so far uncharacterized open reading frames encode methyltransferases acting on 23S rRNA. YbeA is the m³Psi methyltransferase RlmH that targets nucleotide 1915, while YccW is the m⁵C methyltransferase RlmI specific for nucleotide 1962. The experimental analysis was done in collaboration with a group in Odense headed by prof.Stephen Douthwaite (University of Southern Dennmark),

Moreover, researchers from the Bujnicki laboratory analyzed the crystal structure of YccW/RlmI solved by a collaborating group (prof. Jayaraman Sivaraman, University of Singapore) and found that it provides a missing link in the evolutionary history of several different families of methyltransferases that modfy cytosine in DNA or RNA as well as uridine in RNA. They have also identified a new putative RNA-binding domain dubbed 'EEHEE'. This domain is common to RlmI and several other RNA-modification enzymes, including methyltransferases involved in m⁵U formation and in Wye base biosynthesis.

The results of this research has been published in RNA (one article about RlmH) and is in press in Journal of Molecular Biology (two articles about RlmI)


2007 February
R.PabI restriction enzyme reveals a new protein fold and other unusual features

Researchers from the Bujnicki laboratory participated in the discovery of a protein with a new three-dimensional fold. This finding was a result of a collaboration with a group of Japanese researchers headed by prof. Ichizo Kobayashi (University of Tokyo),

R.PabI is a sequence-specific nuclease that cuts DNA within GATC sequences. It belongs to Type II restriction enzymes, proteins that are used as commercial reagents to 'cut and paste' DNA fragments in the laboratory.

R.PabI is unusual (and very valuable) for three reasons: First, R.PabI cuts the DNA to produce a 3'-TA "sticky end" that is unique among restriction enzymes, therefore it can be used for a novel way of 'pasting' of cleaved DNA molecules. Second, unlike nearly all restriction enzymes characterized to date, R.PabI does not require metal ions for its nuclease activity. Third, R.PabI exhibits a new three-dimensional architecture, a feature that is very interesting from the point of view of evolutionary biology and protein folding.

Researchers from the Bujnicki laboratory predicted that R.PabI may exhibit a new type of structure (research published in Nucleic Acids Research, 2005 Jul 21; Vol. 33, No. 13: e112) and collaborated with prof. Kobayashi and his co-workers to analyze the R.PabI structure solved by X-ray crystallography.

Research to be published in Nucleic Acids Research (2007)


2004 December
Polish researchers excel in protein structure prediction

Two groups from the Bujnicki laboratory achieved very high scores in the 6th Community-Wide Experiment on the Critical Assessment of Techniques for Protein Structure Prediction (CASP-6), organized by the Protein Structure Prediction Center.

According to the official rankings for individual categories presented by the expert assessors at the CASP-6 meeting in Gaeta (Italy), the "Kolinski-Bujnicki" group (a duumvirate of Janusz Bujnicki and Andrzej Kolinski from the University of Warsaw) was ranked 1st/2nd (depending on the scoring system) in the New Folds category and 3rd in the Comparative Modeling category. The "GeneSilico" group of students from the Bujnicki lab was ranked 2nd in the Fold-Recognition (Homology) category. Assessors' presentations and detailed evaluations of individual models are available on-line at the CASP-6 website.

In the unofficial ranking compiled by Dr. Jeffrey Skolnick, based on a fully automated assessment of all CASP-6 models regardless of their difficulty, "Kolinski-Bujnicki" and "GeneSilico" ranked 2nd and 5th, respectively.

These scores are similar to those obtained in the previous edition of the experiment (CASP-5, 2002), where "Bujnicki-Janusz" and "GeneSilico" ranked 2nd and 5th in the unofficial overall ranking compiled by Dr. Michael Levitt, with the 1st position in Comparative Modeling for "Bujnicki-Janusz".