Young scientists at #LINO22 – Dark Matter of the Biological Universe

After completing his PhD at the University College Dublin Conor Crawford now works at the Max Planck Institute of Colloids and Interfaces in Potsdam/Germany as Marie Skłodowska-Curie fellow. The topic of his PhD and his current research – despite completely different thematic orientations – are stuck together by sugar. An introduction to the diverse field of glycosciences:

Glycosciences is a field of research where people try to understand the roles glycans (sugar molecules) play in biology. What’s most exciting is that big discoveries and surprises continue to be made and show no sign of slowing down yet. So, plenty of motivation to continue working and having fun with sugars.

Glycans, unlike proteins and nucleic acids, are not template encoded. Which means there are no easy means to ascertain defined structures. This pales in comparison to the ease of which scientists can access nucleic acids, peptides or proteins. This ease of access leads to a wide variety of tools at the disposal of biologists, which naturally leads to an overall better understanding of these biomolecules’ roles in biology.

This is in complete contrast in the glycosciences, where the lack of glycan standards and tools has led to a lack of depth in our understanding. Leading some to even propose that glycans are ‘the dark matter of the biological universe’. This means there is a great unmet need for new tools and technologies in the glycosciences. A big research interest of mine is the chemical synthesis of glycans, which is still a massive challenge, with only a few groups on earth capable of performing this task. Making each new glycan requires a lot of trial and error. For instance, figuring out how to do the final deprotection step on the oligosaccharides, which I made in my PhD, took over two years to figure out. Now in the Max Planck Institute we are trying to develop automated processes to access these biomolecules, which in the long run could help democratise access to glycans.

Understanding Infections Caused by C. neoformans

In my PhD project we attempted to better understand Cryptococcus neoformans biology with a particular focus on its ‘glycan coat’ – termed a capsule (a critical virulence factor) with the intention to contribute to the development of new therapies to advance human health. We used what I would call a ‘chemical biology approach’ that involves diverse disciplines such as synthetic organic chemistry, microbiology and immunology. With this approach we had some success and created vaccine candidates, diagnostics and new tools.

For me, this meant I synthesised and created vaccine candidates in Dublin and then got to travel to Johns Hopkins University as a visiting scholar in 2019 to the lab of Professor Arturo Casadevall, where I helped in the testing of the very vaccines I made in Dublin. My PhD research was recognised with some awards including ‘The ICI Postgraduate Award’ from The Institute of Chemistry of Ireland and The Kathleen Lonsdale Chemistry Prize from the Royal Irish Academy.

Addressing Climate Change

The reason I was drawn to this topic is because some of the biggest challenges humanity is facing currently in the area of climate change. I believe, many of us need to turn our collective attention to this area to create the new fundamental knowledge required to give rise to new innovative technologies. So, then we can use this new technology to offset the worst effects of climate change.

One of the biggest challenges is the level of CO₂ we emit in our everyday lives. And because of this, there is great interest in finding new ways to sequester or ‘sink’ carbon. This is where the marine environment becomes very interesting.

As it is the biggest ecosystem on the planet, covers around 70 percent of the Earth’s surface and is home to some of the fastest fluxes of carbon on Earth. Also, important to mention is that half of CO₂ fixation globally happens in the ocean. However, process is not well described on the molecular level. So now I study it with our collaborators at the Max Planck Institute for Marine Microbiology again in a ‘chemical biology-based approach’.

Amazing Diversity of Glycans

The process we study is called the carbon cycle and it involves all living matter on land and in the ocean. This starts in the ocean by organisms such as algae. These photosynthetic organisms turn the atmospheric CO₂ into an amazing diversity of different glycans (sugar molecules). In particular, I am interested in discovering and investigating how all these different types of glycans present in the ocean are ‘eaten’ or digested by different microbes. A particular interest is looking at the more molecularly complex glycans. As some of these complex molecules require the microbes to have hundreds of enzymes to eat them. In the long run, the knowledge we create can hopefully be the basis for the development of new strategies and technologies that could be useful to take carbon out of the atmosphere.