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Ribosome Structural Biology Lab

Amino acids are assembled into proteins following the genetic instructions encoded in the mRNA in a process called translation. This is primarily governed by a large macromolecular machine called the ribosome. Research in the Fucini and Connell labs focuses on understanding, at a biochemical and structural level, the molecular details of processes that regulate the ribosome at several levels including:1) Inhibition of core ribosomal activities by antibiotics. Medically relevant antibiotics target the ribosome and inhibit its core functions to exert their anti-microbial activities. We aim to understand how these antibiotics interact with and inhibit the ribosome to improve existing drugs or develop novel antibiotics.2) Regulation of core activities like initiation, elongation and termination by native protein factors. During protein synthesis the ribosome has several functional activates which are coordinated by specific protein factors. We aim to understand how these factors work together with the ribosome.3) Ribosome Biosynthesis: Assembling a ribosome requires orchestrating the structural integration of more than 55 ribosomal proteins and three nucleic acid strands in Escherichia coli. This assembly process is facilitated by ribosome assembly factors and we aim to understand how these factors guide the maturation of the ribosome.4) Co-translational folding and protein sorting. The nascent protein is synthesized in the core of the ribosome and passes through a 100Å long conduit to emerge outside the ribosome. This passage is a highly dynamic and 'personalized' event, where the ribosome and the protein chain communicate to regulate the translation and compartmentalization of the nascent protein. We aim to understand the details of this communication.Accordingly, the groups have expertise in the preparation and structural characterization of ribosomal complexes. To provide a complete structural understanding of ribosomal functions we employ complementary structural biology methods like X-ray crystallography, NMR (Fucini Lab) and cryo-EM (Connell Lab).

Main Research Lines: 
Inhibition of core ribosomal activities by antibiotics
Regulation of core activities like initiation, elongation and termination by native protein factors.
Ribosome Biosynthesis