The secrets of fungi: How fungi and human cells share a protein destruction mechanism that can lead to certain cancers

An international team of researchers has studied how the fungus Aspergillus nidulans helps to understand the basics of human molecular biology, writes Dr Özgür Bayram and Dr David Fitzpatrick, Department of Biology
 
The researchers have revealed that fungal and human genomes use similar numbers of genes to encode protein degradation mechanisms.  Although the human genome encodes more than 70 key proteins (F-box proteins) controlling protein degradation, it is difficult to study whole proteins involved in various diseases in humans. Therefore, model organisms such as mice, fungi, worms, yeast are used to understand the complex nature of genetic events.
 
Researchers recently decided to determine F-box proteins and study their function in the highly amenable model fungus Aspergillus nidulans, which helps to understand basics of human molecular biology. They found 74 F-box protein encoding genes, a number that is very similar to that of human F-box genes.
 
Protein degradation controls all vital processes in cells including, cell division and proliferation. In humans, aberrations in protein degradation mechanisms can lead to serious health conditions such as various types of cancers including breast, ovarian, testicular and neuronal cancers. Similarly in fungi, defects in protein degradation mechanisms has been connected with defects in fungal growth and fungal toxin production. However, many functions of the protein destruction system are currently unknown.
 
In addition to being a model organism for human genetics, A. nidulans, is also a model organism to understand genetic regulation of fungal mycotoxin production. Mycotoxins are highly toxic compounds produced by fungi and cause serious diseases in humans and animals. For example, dietary aflatoxins produced by Aspergillus flavus affect more than four billion people worldwide.
 
This is the first systematic analysis of F-box protein-encoding genes of a multicellular organism with a similar amount of genes for F-box proteins as in humans. The researchers found at least 10% of the F-box proteins control important fungal growth and mycotoxin production. Particularly, some F-box genes control sexual development of the fungus with many of these proteins travelling into the nucleus, which is unexpected. Furthermore, the F-box proteins interact with more than 700 key proteins which are involved in cell cycle, stress tolerance and mycotoxin production.
 
In the future, researchers will explore if similar F-box proteins in fungi and humans play equivalent roles in development and growth of humans. Furthermore, future work will also focus on human and plant pathogenic fungi, their F-box proteins and whether they are involved in fungal virulence and pathogenicity in their hosts.
 
The study was part funded by a Science Foundation Ireland (SFI) Career Development Award (13/CDA/2142) and SFI-IRC Pathways programme (21/PATH-S/9444).
 
The findings have been published in one of the leading prestigious journals, PLOS GENETICS.
 
Research was conducted by a team at Maynooth University led by Dr Özgür Bayram and Dr David Fitzpatrick, from the Biology Department, in collaboration with researchers in Germany and Brazil. Research was performed in Dr Özgür Bayram’s Fungal Genetics and Secondary Metabolism (FGSM) laboratory with Dr David Fitzpatrick’s Genome Evolution research group. First author Dr. Özlem Sarikaya Bayram is a junior group leader of Epigenetics Laboratory and supported by SFI-IRC pathways programme (Grant number 21/PATH-S/9444).