Shruthi Ramachandra

Personal Data:
Country of Origin: India
Start of PhD: December 2009
Institution: HKI

PhD Project:
Host pathogen interactions of human-pathogenic yeast

Supervisor(s): B. Hube (HKI), M. Brock (HKI)

Abstract:
Candida albicans is a common member (commensal) of the normal microbial flora frequently found on skin and mucosal surfaces of humans. Under normal circumsdances, the immune system restricts growth of C. albicans and prevents the establishment of infection. However, even minor changes of the microbial flora may cause overgrowth of C. albicans and superficial infections. Furthermore, immunocompromised patients are at high risk of acquiring severe invasive and disseminated infections with C. albicans (candidiasis).
As a commensal and during infection, C. albicans needs to acquire nutrients from the host to gain molecules and energy for growth and persistence. In addition to carbon sources, nitrogen sources are essential for growth and persistence. C. albicans produces several secreted aspartic proteases (Saps), which can degrade host proteins and play an important roles during the infection process. Peptides and amino acids released by Sap activity are transported via oligopeptide and amino acids permeases into the fungal cell and can be used as both carbon and nitrogen source during infection. However, is is not clear, how nitrogen sources are sensed, taken up and metabolised.
In this project, sensing, uptake and utilisation of nitrogen sources by C. albicans will be investigated. Growth experiments, gene expression studies, gene deletions and phenotypic analyses of deletion mutants will be applied to get insights into the mechanisms by which C. albicans can sense and metabolise nitrogen sources. Furthermore, this project will help to identify the most important nitrogen sources of C. albicans during host infection.