FPI2015, Structures of Bacteriophage Proteins

Proposal for predoc project (FPI associated with granted project BFU2014-53425-P or Severo Ochoa plan CNB; or other financing calls)
Our group is looking for motivated PhD candidates for the following project.

Structural biology of bacteriophage fibres, tailspikes and endolysins
Antibiotic resistance in pathogenic bacteria is on the rise. At the same time, the discovery of new antibiotics has been slowing down, which means other options to specifically detect and combat pathogenic bacteria have to be explored. Bacteriophages and their derived proteins are one such option. Bacteriophage tail fibres may be used to detect bacteria, while their cell-wall degrading proteins may be used to weaken or kill them. The project involves solving the high-resolution structures of these bacteriophage proteins by X-ray crystallography, if possible in complex with their binding partners and substrates. During the last few years we have solved the structures of the homo-trimeric receptor-binding domains of the bacteriophage T4, T5 and T7 tail fibres - one of each of the Myoviridae, Siphoviridae and Podoviridae. Each of these proteins presented new folds and suggested which parts of the structure are involved in receptor binding. We have also identified oligosaccharide receptor analogues for them.
Bacteriophages express enzymes during their infection cycle that target their host bacteria in different ways. Examples are receptor-binding tailspikes that hydrolyse outer cell wall components so the phage can access the membrane in the first step of infection, and endolysins to digest the bacterial peptidoglycan layer in order for the bacteriophage progeny to escape from the cell. During the last year, we have solved the structure of the CHAP domain of the Staphylococcal lysin produced by bacteriophage K. Targets are endolysins of several pathogenic bacteria. The atomic structures of the enzymes will allow detailed understanding of their action and mechanism and may suggest site-directed mutations to alter their activity and host specificity.

Structures of gp37 of the myovirus T4 (left), pb1 with and without its chaperone domain of the siphovirus T5 (middle) and gp17 of the podovirus T7 (right).
Interested candidates that fulfil the conditions of the FPI call, please contact as soon as possible (before 22 June; deadline FPI call is 29 June 2015): Mark van Raaij, CNB-CSIC, Madrid; http://www.cnb.csic.es/~mjvanraaij
E-mail: mjvanraaij en cnb.csic.es, tel. 91 585 4616
Call (in Spanish): http://www.boe.es/diario_boe/txt.php?id=BOE-A-2015-6508