Characterization of mitochondrial and ER dynamics during Brucella infection – charM-Ed

Many bacterial pathogens can highjack the endoplasmic reticulum (ER) to promote intracellular replication. This is the case of Brucella spp., which uses a type IV secretion system (T4SS) to sustain interactions with the ER enabling formation of a replicative compartment. Brucella infection has been shown to induce ER stress, which benefits intracellular replication but is also associated with inflammation and induction of abortion, hallmarks of brucellosis. The molecular mechanisms in these processes still need to be unravelled. We have identified a Brucella effector, named BspL, injected by T4SS into host cells during infection that targets the ER and mitochondria. We have identified its cellular target, HERP1 a key regulator of ER stress and cellular homeostasis. The goals of charM-Ed are to: 1) carry out an in depth characterization of BspL; 2) to define the role of its cellular target in Brucella infection by establishing how its interaction with BspL may be altering ER functions and mitochondrial dynamics. Overall, this fundamental research project will not only characterize the function of a newly identified Brucella effector but will also establish for the first time a role of HERP1 in bacterial pathogenesis. In addition, this project will help further elucidate HERP1 functions, which is implicated in cancer and several chronic neurodegenerative disorders including Alzheimer’s, Parkinson’s, and Huntington’s diseases.