Prof. Sheng-Ce Tao
Project Description and Objectives
Tuberculosis (TB) ranks highest in infectious diseases measured by direct and indirect mortality. Mycobacterium tuberculosis (Mtb) is the single causative agent of tuberculosis, which caused 9.6 million newly identified active cases, and 1.5 million deaths from the disease in 2014. Moreover, the emergence of multidrug resistant (MDR) and extensively drug resistant (XDR) strains of Mtb has increased the threat that this disease imposes to global public health. Therefore, it is urgently required to develop effective vaccines and drugs for reducing the global burden of TB. Discouragingly, the progress in discovering and characterizing appropriate vaccine candidates and drug targets has been severely impeded by a general lack of knowledge about Mtb biology and its regulation.
For Mtb, the ribosome is one of the most important targets for antibiotics development. Though the core structure of the bacterial ribosome is similar to that of eukaryotes, there are significant differences of the overall structure and regulation mechanism. Because of this, the bacterial ribosome has been used as the direct target for drug screening. In turn, there are a variety of effective antibiotics that target the ribosome directly thus disrupting the bacterial protein synthesis machinery. Some examples of antibiotics that follow this mechanism are aminoglycoside, macrolides and tetracyclines. However, there are limited studies about ribosome regulation; the ribosome regulation mechanism is still not well studied. This is the bottleneck of ribosome specific antibiotics development. It is not just a challenge, but also a chance.
In consideration of the urgency of the above situation, we will try to reveal the ribosome regulation systematically through global protein-protein interaction discovery. By using bioinformatics analysis and initial validation, and function studies, we aim to identify 1-2 Mtb specific ribosomal protein-protein interactions as potential drug targets.
The objectives of the project are: 1. Construct the first protein-protein interaction network for all the Mycobacterium tuberculosis (Mtb) ribosomal proteins.2. Identify 1-2 Mtb specific ribosomal protein-protein interaction as potential drug targets.
Clone 2-3 ribosomal genes
Expression 2-3 ribosomal proteins
Profile the global protein-protein interaction using the proteome microarray
Construct a protein-protein interaction network for at least one ribosomal protein