When Staphylococcus aureus cells form a biofilm in the human body they become shielded from the immune system and highly resistant to antibiotics. Current therapeutic options against biofilms are limited to the long-term application of a combination of several antibiotics in high doses or the surgical removal of infected tissues.
The student will study the mechanisms that phages from the family Myoviridae, natural predators of bacteria, have evolved to infect biofilms to identify new strategies for the development of antimicrobial compounds or phage therapy. He/she will use focused ion beam milling in combination with cryo-electron tomography (cryo-ET) and single particle reconstruction methods to study the replication cycle of phage phi812 in S. aureus cells growing in a biofilm. He/she will complement the inherently static cryo-electron microscopy analyses with time-resolved light sheet fluorescence microscopy observations of the spread of the phage infection within a biofilm. Phi812 is a potential phage therapy agent for the treatment of antibiotic-resistant S. aureus infections.
Keywords: bacterial biofilm, phage therapy, ion beam milling, cryo-electron tomography, fluorescence microscopy, cryo-electron microscopy, virology, antibiotic-resistance
Viruses from the Enterovirus genus belong to the family Picornaviridae of human and vertebrate pathogens. Diseases caused by enteroviruses range from upper and lower respiratory tract infections to life-threatening encephalitis. Rhinoviruses are responsible for 40% of the common cold cases that result in yearly cost of tens of billions of US$ in treatments and lost working hours worldwide.
The student will study the replication cycle of enteroviruses (represented by human rhinoviruses A2 and B14 and enterovirus 71) in vivo by a combination of focused ion beam milling and cryo-electron tomography. He/she will investigate the mechanism of enterovirus genome release and delivery into a host cell, changes in intra-cellular organization induced by enterovirus infection, and the assembly of progeny virions. We will complement the whole-cell studies by high-resolution cryo-electron microscopy of virus genome release under biologically relevant conditions in vitro.
Keywords: enteroviruses, replication cycle, ion beam milling, cryo-electron tomography, cryo-electron microscopy, virology