Background and current state of research
Part of the project work is also done within project 5 of the DFG Research Unit 5042.
Originally Hexokinase has been known for its metabolic role acting as a pace-maker enzyme in glycolysis. HK2 which is one of the 4 isoforms of Hexokinase was recently found to be involved in inflammation and cancer.1 In macrophages and dendritic cells Hexokinase binds N-Acetylglucosamine (NAG) which is a component of Peptidoglycan in bacterial cell walls. In the following the NLRP3-inflammosome gets activated and mediates the expression of proinflammatory cytokines such as IL1-ß and IL-18.2
Lately it also has been found out that the intestinal microbiome regulates the expression of Hk in intestinal epithelial cells (IEC).3 A gram-negative bacterium could be identified as a specific inductor. This leads to the assumption that species-specific mechanisms exist which regulate Hk-expression
1 Patra et al. "Hexokinase 2 Is Required for Tumor Initiation and Maintenance and Its Systemic Deletion Is Therapeutic in Mouse Models of Cancer" Cancer Cell 24, pages 213–220, August 12, 2013
2 Wolf et al. "Hexokinase Is an Innate Immune Receptor for the Detection of Bacterial Peptidoglycan." Cell 166, pages 624–630 , July 28, 2016
3 Sommer et al. „Site-specific Programming of the Host Epithelial Transcriptome by the Gut Microbiota” Genome Biology, published online, March 38, 2015
Our goals
Our goal is to understand the interactions between the intestinal microbiome and Hexokinase. We want to identify species of bacteria and factors which influence the expression of this enzyme. Afterwards we may be able to for example characterize beneficial types of bacteria.
How to get there
To identify species of bacteria which interact with Hexokinase we will analyze the
microbiome of KO- and WT-mice by 16S-RNA-analysis. Additionally, we will investigate regulation of Hexokinase in multiple in vitro approaches.