PhD Proposal: Alex Doan

Alex Doan, PhD Student

Advisor: 

Dr. Mark Marten

TITLE: Molecular Mechanisms of Echinocandin-Induced Hyperseptation:  Mapping Protective CWI-SIN Crosstalk in Aspergillus nidulans 

ABSTRACT: 

Echinocandin resistance poses a major challenge in clinical mycology.  Alongside azoles, amphotericin B, and flucytosine, echinocandins are one of only four known therapeutic options available to treat systemic mycoses - diseases that claim an estimated 3.75 million human lives annually.  Resistant fungi include filamentous species such as Aspergillus fumigatus, that draw their resistant properties actively through the formation of septa.  

Septa are structures that subdivide hyphae following nuclear division and allow for compartmentalization of cytoplasm. While their formation is tied closely to the cell cycle, it is a dynamic process, regulated by the septation initiation network (SIN), that can be upregulated in response to cell-wall stress, limiting the e ectiveness of cell-wall targeting fungicides, such as the echinocandin micafungin. 

A cellular signaling pathway driving the hyperseptation response to cell-wall stress has yet to be defined.  In Chelius et al. (2020), analysis of the dynamic-phosphoproteomic response to micafungin treatment revealed that the downstream SIN kinase, SidB, was di erentially phosphorylated.  A subsequent dynamic phosphoproteomic study on a strain lacking the terminal kinase of the cell-wall integrity (CWI) pathway, MpkA, found that SidB was no longer di erentially phosphorylated under micafungin treatment, indicating that CWI drives SIN activity and that MpkA specifically is required to activate SIN. 

Agenda

• 8:55 pm: Meeting room will open
• 9:00 pm: 45-min presentation will be open to the public with Q&A.
• Followed by a closed session with the committee and PhD Student.