The School of Molecular and Cellular Biology at the University of Illinois at Urbana-Champaign

Modulation of host cells and tissues by bacterial toxins
Many pathogenic bacteria generate protein toxins that modulate properties of host cells and tissues in order to create a more suitable niche for colonization and, in some cases, to persist for extraordinary periods of time. We are studying the cellular intoxication mechanisms and structure-function relationships of several toxins that, to be successful, must traverse the membrane barrier into human cells. We are especially interested in investigating mechanisms of cellular entry and trafficking, as well as the action of toxins on immune cells. Current model systems in the laboratory include the vacuolating cytotoxin (VacA0 from Helicobacter pylori, the cytolethal distending toxins, and a novel toxin we have recently discovered from Helicobacter pylori.

Molecular and cellular basis of chronic bacterial infections
There is particular interest is in understanding mechanisms that allow pathogenic organisms to persist within the host during chronic infection. An emerging paradigm is that persistent organisms are highly adaptive because they have co-evolved with their hosts. As a model system, the Blanke Laboratory is focusing on persistent infection in humans with the gastric pathogen, Helicobacter pylori, which is a significant risk factor for the development of gastric ulcer disease and stomach cancer. Because nearly half the world's population is infected with H. pylori, and because of increasing antibiotic resistance, gastric diseases caused by these micro-organisms are an important biomedical problem. Current research is focused on the contributions of a bacterial toxin (VacA) produced by H. pylori towards remodeling the host environment to create a more suitable niche to colonize and persist for the lifetime of the host in the absence of medical intervention. In addition, there is ongoing research to identify mechanisms by which H. pylori organisms are remodeled to become more adaptive to the stomach. These mechanisms include the capacity of H. pylori to sequester host cholesterol, and to change very rapidly to adapt to changes within the stomach.

Intracellular lifestyles of pathogenic bacteria
We are investigating mechanisms by which pathogenic bacteria not only survive encounters with host immune cells, but are able to exploit these cells by entering, surviving, and in some cases, replicating and escaping. Our model system is Bacillus anthracis, the causative agent of inhalation anthrax. The Blanke laboratory, along with several other laboratories, has been investigating the mechanisms by which B. anthracis enters the human lung and exploits the immune response in order to cause disease. Current work centers on the interaction of B. anthracis spores with human cells, and the capacity of B. anthracis to exploit the intracellular phagolysosome environment to germinate and replicate.

Induction of "limited damage" within the host
We are interested in strategies used by pathogenic bacteria to limit damage within the host as a strategy for promoting infection or persistence. We are focusing on mechanisms by which pathogenic organisms are capable of manipulating the human cell cycle through the action of a relatively new family of bacterial toxins, called the cytolethal distending toxins. We are investigating the cellular intoxication mechanisms, structure-function relationships, and evolutionary relationships between these toxins.

Complex Infections
The Blanke Laboratory has undertaken research, associated with the IGB Host-Microbe Systems Theme, to study the dynamic interactions between the host and its commensal as well as pathogenic microbes to elucidate basic processes of disease and commensalism. This research will initially focus on the complex ecosystem of the vaginal microbiota and its impact on health and disease in women. As part of the HMS Theme, the Blanke laboratory is involved in the development of analytical and functional genomic techniques for determining the microbial and immunological content of the vaginal ecosystem and for identifying specific host biomarkers in response to colonization with normal versus abnormal microbes, as well as toxicity or infection.

Development of molecular countermeasures targeting pathogenic bacteria
The ultimate goal of the basic science conducted within the Blanke laboratory is to develop new countermeasures against pathogenic organisms. Current projects, which are highly collaborative, target B. anthracis, the botulinum neurotoxins, the cytolethal distending toxins, VacA, and H. pylori.