A Mathematical Model of the Iron Regulatory Network in Aspergilus Fumigatus

Aspergillus fumigatus is an opportunistic fungal pathogen responsible for invasive aspergillosis in immunocompromised individuals. Current detection and treatment strategies for invasive aspergillosis, as well as other invasive fungal infections, are poor. Iron has been shown to be essential for Aspergillus fumigatus virulence. Furthermore, mechanisms in the iron regulatory network are believed to be potential drug targets since iron management in fungi is vastly different from that in mammals and other eukaryotes. Therefore a better understanding of iron homeostasis in Aspergillus fumigatus could help improve drug therapies for invasive aspergillosis. In this research a discrete model of iron uptake, storage and utilization in Aspergillus fumigatus with particular focus on siderophore-mediated iron acquisition is constructed. The model predicts oscillations in gene expression as the fungus adapts to a switch from an iron depleted to an iron replete environment. The model is validated via in vitro experiments.

Name thesis:degree_name

Master of Science

Level thesis:degree_level

masters

Discipline thesis:degree_discipline

Mathematics

Department dc:contributor.department

Mathematics

Grantor dc:publisher

Virginia Tech

Year dc:date.issued

2013

Author dc:creator

• Brandon, Madison Gayle

Chair dc:contributor.committeechair

• Laubenbacher, Reinhard C.

Committee members dc:contributor.committeemember

• Ciupe, Stanca M.
• Lawrence, Christopher B.

• Aspergillus fumigatus
• discrete model
• iron regulation
• siderophores
• gene regulatory netwrok
• genetic oscillations
• qRT-PCR

Statement dc:rights

• In Copyright

Licence dc:rights.uri

• http://rightsstatements.org/vocab/InC/1.0/

Dc Identifier Other

vt_gsexam:923

OAI identifier oai:identifier

oai:vtechworks.lib.vt.edu:10919/23086