What fungi can do: transcription regulation in microscopic mushrooms

30 September 2016

From the mould we find on stale bread to mushrooms in soup to the billions of invisible spores floating through the air at any given moment, fungi surround us. While usually an unwanted guest in the home or sometimes even a deadly infection in the body, fungi have been food and medicine for humans for thousands of years. Less well studied and understood than other higher organisms, fungi have a lot more to offer us- if we know where (and how) to look.

At the new campus of the University of Macau, Dr Chris Koon Ho Wong (Croucher Fellowship 2009) is studying transcription regulation in fungi, with broad-reaching potential from medicine to food production to alternative fuels.

Regulating transcription

Transcription is the process by which genetic information is copied from DNA to create RNA so that it can later be read and processed to build proteins.

Every biological function is locked in the genome and the first step to unlock that information is transcription.

The regulation of transcription is crucial as the mechanisms in place keep genes from being expressed at the wrong times, or in the wrong place. 

For example, a gene for the production of pigment needs to be activated in skin cells, but not in bone cells. Thanks to recent advances in molecular biology, it is now possible to more accurately look at the way transcription factors (these gene "switches") bind to and interact with DNA.

As cancer is often caused by errors in regulation, a comprehensive understanding of the underlying mechanisms of transcription regulation may lead to the development of more advanced cancer treatments.

Whether the mutation leads to overproduction and stimulates cells to grow in excess or it causes a loss in the cell’s growth checkpoints, keeping it from arresting its proliferation when necessary, precise regulation of many transcription factors is highly important in cancer prevention and treatment.

Many transcription regulation mechanisms are also highly conserved throughout eukaryotes. In fact, most were first identified in fungi, meaning that a genetic on/off switch in mould may be able to tell us something about a similar switch in humans. Fungi make a great model to study transcription regulation because of their ease of handling and manipulation and the extensive amount of tools available.

The world of fungi

“Fungi are very smart, they know how to use resources really well,” says Wong. In the wild, fungi live in very competitive environments; competing with scavengers to get the most resources out of very difficult conditions.

Because of this, they need to process resources as efficiently as possible. Fungi are able to sense their surroundings and know which resource is best and should be consumed first. Once the most efficient resource has been consumed, they’ll switch off the genes that code for enzymes necessary to process it and move on to the next most efficient resource, switching on the genes to consume that resource instead.

Button mushrooms on our plates, Gliocladium-produced ethanol in our gas tanks, penicillin in our medicine, fungal products are everywhere. When it comes to use in industry, fungi are incredibly versatile. “They can do a lot of cool and interesting things and they can do a lot of nasty things; we actually only know a small amount about them,” says Wong.

And it’s certainly true that fungi are capable of many things that could change the world. The story of penicillin is a classic one, the accidental discovery of a mould that changed medicine. Microscopic fungi with the ability to generate fuel compounds are being found from Patagonia to Japan. And with production in mind, efficiency becomes the goal.

Advances in biotechnology have made the genetic engineering of microorganisms easier than ever and Wong’s research into the basics of molecular machinery is the first step into perfecting these little fungal factories.

While many of the forms of fungus we encounter day to day are totally harmless, many species of fungi are also potentially pathogenic. From spoiled food contaminated by Aspergillus to the deadly Amanita mushroom growing on the forest floor, mycotoxin-producing fungi are a common source of sickness and even death.

Understanding the regulation of transcription activity during infection sheds light on not only how fungal pathogens work but also how to stop an infection.

Aspergillus niger

“Every biological function is locked in the genome,” says Wong, “and the first step to unlock that information is transcription.” If we know what genes are being turned on, we know what the fungus is trying to do when it infects a host.

Bioinformatics

In addition to his work on transcription regulation, Wong’s “dry lab” does a lot of bioinformatics analysis, taking advantage of the developments in the field of Next Generation Sequencing and Genomics made in recent years.

Thanks to the speed and power of next generation sequencing (NGS), huge amounts of data are churned out by Wong’s wet lab regularly.

With help from dry lab researchers specialising more in bioinformatics analysis, researchers working on the bench are able to process and extract crucial information from the massive amounts of data put out by the powerful NGS machines. Using their complementary expertise, the wet lab and dry lab researchers work together to address questions with a genomics and bioinformatics based approach.

Wong hopes that his team can contribute their findings and knowledge in fungal transcription regulation to the field.

At the University of Macau, Wong’s team is already sharing their knowledge with other research groups both within the Faculty of Health Sciences and out.

As a lot of the technology surrounding NGS is quite new, it will still be a matter of time until greater knowledge of bioinformatic analysis is spread and the NGS machines themselves are more readily available.

But with experience in NGS and bioinformatics under his belt, Wong is able to provide both advice and consultation in addition to facilitating the actual sequencing process.

“If a team is interested in RNA sequencing, we help them find the best way,” says Wong, “and if they don’t know how to do it, we find someone who can help teach them.”

In addition to the sequencing itself, Wong’s dry lab team also provides bioinformatics analysis services to help other researchers who may be less familiar with the technique to get the most out of their data.

The sequencing and data processing remains both expensive and technically difficult, leaving many research teams unable to take full advantage of its potential. As most of the NGS technology is new, having a someone like Wong with more familiarity in the field will help encourage other researchers to explore what bioinformatics analysis is capable of, hopefully leading to breakthroughs from teams who may have previously been unable to tap into the power of bioinformatics.

Whether it’s foundational research in transcription regulation or exploring and promoting the limits of bioinformatics analysis, Wong and his team hope to share their knowledge. The potential for both these areas is immense, and through collaboration and free exchange of ideas some of that potential can be realised.

Wong received his B.Sc.(Hons) and Ph.D.(Genetics) degrees from The University of Melbourne, Australia. He graduated with First Class Honours and on the Dean’s Honour List. He received several scholarships and awards for his outstanding academic achievements. In 2008, he moved to Harvard Medical School for his post-doctoral research, and was awarded a Croucher Fellowship in 2009. He is now Assistant Professor at the Faculty of Health Sciences at the University of Macau.

To view Wong’s personal Croucher profile, please click here.