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Research team

Bioinformatic team SEQUOIA
LIFL, Université Lille 1 / INRIA Lille Nord-Europe

The SEQUOIA team is developing algorithms and software to analyze biological sequences: DNA, RNA and proteins. Our skills are sequence alignment, non-coding RNA, nonribosomal peptides, genomes organization and comparative genomics.

Supervisor

Maude Pupin [www]
maude.pupin [@] lifl.fr, 03 59 57 79 19

Topics: bioinformatics, graph algorithm, nonribosomal peptides

Fixed term period : 4 to 6 months, beginning in 2010. Candidatures ouvertes.

Requirements: good skills in algorithms, knowledge in biology or bioinformactics not needed.

Scientific context

Nonribosomal peptides (NRPs) are synthetized by huge enzimatic complexes called dynthetases (refs 1 and 2). Those peptides show a great structure variety: they can contain branches and/or cycles. They also are constituted by non rpoteogenic amino acids (more than 500 were observed till now). The NRPs possess various biological activities such as antibiotic, immunosuppressor and can be used in various domains. The SEQUOIA team, in collaboration with ProBioGem laboratory from Lille University, has developped the first and unique database dedicated to those peptides, called Norine (cf ref 3). It contains several tools to analyse and manipulate those peptides: strutural or monmeric search ; peptide structure visualization and drawing.

Proposal

As the nonribosomal peptides are not always linear, we represents them as labelled non oriented graphes. The nodes represent the amino acids and the labels their names. The edges represent a chimical bond between two amino acids.
We already developped an efficient algorithm to search for a structural motif in a set of peptides (cf ref 4). This algorithm was adapted to compare two peptides
The work goal is to extend the actual comparison of two graphes to the comparison of several ones. This multiple comparison will be limited to similar graphes so that the search space will be reduced.
To begin, the student will study peptide famillies extracted from Norine database to make a list of the different cases encountred. This will help in defining the errors tolerated in the algorithm.
Then, the student will concieve and develop the algorithm for multiple comparison of graphes, taking into account the constraintes defined previously.

References

1. D. Konz, M. Marahiel. How do peptide synthetases generate structural diversity ? Chemistry & Biology, 1999, 6 (2), R39-R48
2. H. Mootz, D. Schwarzer, M. Marahiel. Ways of assembling complex natural products on modular nonribosomal peptide synthetases. ChemBioChem, 2002, 3(6), 490-504
3. Ségolène Caboche, Maude Pupin, Valérie Leclère, Arnaud Fontaine, Philippe Jacques, and Gregory Kucherov. NORINE: a database of nonribosomal peptides. Nucleic Acids Research, 2008, 36, D326-D331
4. Ségolène Caboche, Maude Pupin, Valérie Leclère, Philippe Jacques and Gregory Kucherov. Structural pattern matching of nonribosomal peptides. BMC Structural Biology 2009, 9:15