Nicole Hauser

Project title

Combating Antibiotic Resistance Chemo-Enzymatically with Nature-Inspired Scaffolds

What is your project about?

Each year, infections caused by multidrug-resistant bacteria claim more than one million lives worldwide, and the number continues to rise. Yet Nature still holds largely untapped potential. Many bacteria, fungi, and plants produce so-called natural products with antibiotic properties. Unfortunately, some of these compounds have undesirable side effects that limit their clinical use. This project explores how two natural products with promising activity against resistant bacteria, but problematic side effects, can be modified using a combination of chemical methods and enzymes, Nature’s own catalysts. By developing an efficient strategy for producing and refining these compounds, the project aims to pave the way for new classes of antibiotics that are both effective against multidrug-resistant pathogens and free from harmful side effects.

How did you become interested in your particular field of research?

In high school, I took part in a research week at ETH Zürich, where I discovered my interest in chemistry through both hands-on laboratory work and theory. As a student, I became particularly interested in chemical reactivity and how this understanding can be applied across diverse contexts. When I learned about enzymes, Nature’s own chemical tools, I was captivated and chose to pursue this area further after my PhD. As a postdoctoral researcher, I worked in an interdisciplinary environment focusing on enzymes, natural products, and the microorganisms that produce them. Today, I combine classical chemistry and biocatalysis to make chemical processes more sustainable and to enable the synthesis of complex molecules that contribute to societal wellbeing.

What are the scientific challenges and perspectives in your project?

The natural products that we use as starting points are glycosylated, meaning they contain sugar units. In-stalling these sugar groups is chemically challenging and typically requires the use of protecting groups, which increases the number of synthetic steps and the amount of waste generated. Enzymes can perform these transformations selectively, but they rely on activated sugars that are usually unstable. We have developed a method to stabilize these activated sugars, enabling more efficient production of glycosylated natural products. The project is expected to demonstrate the potential of this approach and con-tribute to more sustainable strategies for glycosylation in the future.

What is your estimate of the impact, which your project may have to society in the long term?

My research aims to make chemical synthesis, for example in drug development, more sustainable by combining enzymes with classical organic chemistry. This approach can reduce the use of hazardous chemicals, minimize waste, and improve energy efficiency. In the long term, it may contribute to a greener chemical industry and more sustainable production of important compounds. Our work also addresses broader societal challenges such as antibiotic resistance, as improved access to complex natural products can support the development of new medicines. Overall, this research has the potential to contribute to both environmental sustainability and human health.

Which impact do you expect the Sapere Aude programme will have on your career as a researcher?

The Sapere Aude grant will be pivotal for my further research career by enabling me to consolidate and expand my independent research group. The grant will allow me to build and lead a strong team of researchers, as well as attract talented students and collaborators. In addition, the grant will strengthen my scientific independence and give me the freedom to pursue new ideas and more ambitious projects. Altogether, it will support the development of my profile as a research leader and help position me internationally within my field.