Can cockroaches help us cure tularemia?

By Niharika

Biology Medicine

Pledged

Rs 0

0%
Funded
Rs 80,000
Goal
Campaign Expired

About This Project

Tularemia is a deadly disease caused by the bacterium Francisella tularensis (Ft). This bacterium is also a potential biological weapon. In order to develop cures, we need to know more about how Ft avoids the host immune system. For my senior thesis, I will use cockroaches (which have a strong immune system) to test my hypothesis about why certain chaperone proteins are required for disease. This may lead to better treatments in the future.

What is the purpose of the research project?

The ClpB and ClpX chaperone proteins are required for F. tularensis (Ft) to cause disease.These chaperones control turnover of proteins in the cell and help Ft adapt to stressful conditions that could destabilize proteins by causing them to fold incorrectly. Studies have demonstrated that without ClpB, Ft is sensitive to extreme heat. But, we don’t think that this observation fully explains why it is required for disease. The mutant also establishes an initial infection in mice but is unable to persist and multiply at later time points. These findings indicate to us that there is a specific pathway, required for late-stage infection that is inoperable or impaired in the clpB mutant. Identifying this important pathway could lead to new treatments for tularemia.

What is the significance of this project?

In addition to their role in protecting from heat stress, chaperones are vitally important to mutation tolerance in bacteria. This is especially true for intracellular pathogens that accumulate high rates of damaging mutations due to the combined effects of genetic drift and repeated population bottlenecks during transmission. Chaperones can protect other proteins from these damaging mutations. I hypothesize that this is how ClpB helps Ft cause disease. I think ClpB stabilizes another protein that can't fold properly by itself and that without this other protein, Ft can't cause disease. ClpX may be playing a similar role. If my hypothesis is correct, future treatments for tularemia may target the ClpB- and ClpX-dependent proteins that my project will identify.

What are the main research goals of the project

I will test my hypothesis by comparing gene expression patterns in normal Ft, the ClpB mutant, and the ClpX mutant at early and late time points during infection. I predict that I will see a lot of differences. But, I am specifically looking for a couple things.First, pathways (sets of related genes) that are activated only in normal Ft, but not in one of the mutants, may indicate that an important regulator is stabilized by ClpB or ClpX.Second, pathways activated to a higher level in the mutants may indicate that another pathway with similar biological function isn't working properly, because an important component needs ClpB or ClpX.I will then use Bioinformatic analysis of the mutation patterns of these pathways to identify which components are likely to be stabilized by ClpB and ClpX.

Budget


Target Amount: 80000

Rs. 15000 in Bacteriological media

Rs. 5000 in Disposables

Rs. 60000 in Library prep and sequencing

Meet the Team

Graduate Student at Madras State University
Backers