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Q&A with The Lipidomics Team

What was your role within the team?

Jeffrey Buter: I contributed to the Lipodomics team during my PhD (with Minnaard) and Postdoc (with Moody). Both supervisors provided me with the tremendous opportunity to receive education in two distinct fields of science, which was a great training ground for a young academic.

Jeroen Codee: The design and synthesis of complex mycobacterial glycolipids. To this end different synthetic groups contributed, each with their own expertise (glycans and lipids) to enable the assembly of a unique library of mycobacterial glycolipids (now available to the wider research community through the Bill and Melinda Gates lipid bank).

Nicole van der Wel: The role of the Amsterdam team was to visualize the effects of the purified lipids and glycolipids on host cells and the mycobacteria using high resolution Electron Microscopy techniques. As the electron microscope can visualize details within cells and bacteria, this technique was really suited for the study on the impact of bacterial lipids on cells.

What were the biggest challenges in this project?

Jeroen Codee: There were many, as would be expected from a large collaborative project. The synthetic challenges came from the complexity and diversity of the different forms of the glycolipids. It has required to combined expertise of different synthetic groups to assemble the library of complex glycolipids.

Nicole van der Wel: The work we do aims at the development of treatment or vaccines for Mycobacterium tuberculosis infections and these bacteria are very difficult to eradicate. We see that after the corona crisis, the number of TB patients increases again and in 2023, TB returned to being the world鈥檚 deathliest infectious disease. Even after more than a century of TB research we have not been able to combat this horrible infectious disease.

What different strengths did different people bring to the team?

Jeroen Codee: The team brought together expertise in many different areas, ranging from synthetic organic chemistry, structural biology, cellular biology, immunology to clinical knowledge.

Nicole van der Wel: We collaborate with very different types of researchers, from immunologists, organic chemists till microscopists. The microscopy allows us to visualize cells in high detail, showing for example how cells respond to a bacterial infection or treatment with a single bacterial lipid or how bacteria respond to deletion of lipids. That allowed the team to understand the biological effect of the individual, purified lipids.

Why is this work so important and exciting?

Jeffrey Buter: For decades now, tuberculosis has killed millions of people, and it continues to do so. Although we know a lot about the bacterium, there is still much to unravel in order to find develop new antibiotics, treatments, vaccines, as well as cheap diagnostic test that can be deployed in low-income point-of-care health clinics.

Jeroen Codee: For our part of the team, it shows the value in generating well-defined, pure molecules. The development of new synthetic chemistry has paved the way to the assembly of complex mycobacterial glycolipids. In a unique collaboration different synthetic chemistry groups joined forces to generate a unique library of mycobacterial glycolipids, which is now available to the wider scientific community. The use of the pure and single molecules has enabled us to precisely dissect their role in the pathogenesis of mycobacterial infections. Most of these lipids cannot be retrieved from natural sources in pure enough form.

Nicole van der Wel: Our rather fundamental research has been picked up by various partners who now try to translate our research to diagnostic tools. We have also identified a possible host-based therapy and are further investigating this with partners.

Where do you see the biggest impact of this technology/research being?

Jeroen Codee: The work will have impact on many different areas: the new synthetic chemistry used will find application in the synthesis of many other glycans, lipids but also other biomolecules. The generated glycolipid library will be used to uncover many other (unforeseen) activities for the compounds, and the compounds are currently being further developed as components of potential new vaccines (as antigens or adjuvants with a unique mode of action).

Nicole van der Wel: The work on TB has impact on the scientific community for better understanding of and accessibility to the lipids that are crucial for this infectious disease. But even more importantly, our work should impact the TB patients who can be faster diagnosed and hopefully given a better vaccine than the current vaccine.

How will this work be used in real life applications?

Jeffrey Buter: The discovery of new molecules, their biosynthesis, and their role in disease, really sets the stage for the development of novel antibiotics as well as vaccines.

Jeroen Codee: The molecules can be part of new synthetic vaccines and adjuvants in the prevention of mycobacterial infections.

Nicole van der Wel: Ultimately TB patients can be faster diagnosed and hopefully given a better vaccine than the current vaccine.

How do you see this work developing over the next few years, and what is next for this technology/research?

Jeroen Codee: New activities will be uncovered for the generated lipid library and the mode of action can now be established at the atomic/molecular level through structural studies. This will open up new possibilities to combat mycobacterial infections.

Nicole van der Wel: The role of lipids and glycolipids in TB infections are very unique and not well understood and with collaborations like ours we will be better describe and understand this field. Thus far treatments directed towards the lipid balance between host and pathogen are not used as a therapeutic target, we are together with more researchers over the world, are moving towards that.

What inspires or motivates your team?

Jeffrey Buter: I think we are all motivated to create impact on tuberculosis research, so the noses are pointing in the same direction. There is great respect between the collaborators and the collaboration is not motivated by self-interest.

Jeroen Codee: The complexity and beauty of natural molecules, in this case the complex mycobacterial glycolipids. Why do these bacteria generate these fascinating and specific molecules? How do they do that? How do these molecules shape host-pathogen interactions?

Nicole van der Wel: Seeing is believing, microscopy has strengthened and improved many different research projects and specifically in collaborations, we flourish. This consortium has been especially good as the team consist out of very different and all very good collaborators that together produce very novel and exciting data which we can further strengthen with our microscopy images.

What is the importance of collaboration in the chemical sciences?

Jeffrey Buter: Speaking for us I think it鈥檚 fair to say that without our collaboration our individual research would have not been as impactful as what we achieved together. The saying 鈥渢he whole is greater than the sum of its parts鈥� definitely applies to our consortium.

Jeroen Codee: The importance of collaboration cannot be stressed enough. At the same time it is vital to acknowledge that advances in a mono-disciplinary areas are all-important to drive collaborations.

What does good research culture look like or mean to you?

Jeffrey Buter: Without a good research culture, collaboration is not sustainable in the long-term. It is a vital component.

To me, a good (collaborative) research culture means: 1) mutual respect, 2) interest in, and understanding of each other鈥檚 fields of research, and 3) open and honest communication.

Jeroen Codee: It should be open and shared to bring as much mutual inspiration and knowledge exchange.

Nicole van der Wel: An open atmosphere where researchers can share their data and ideas so that different fields and approaches will improve and motivate the others so that we all work more efficiently towards a common goal.

What advice would you give to a young person considering a career in the chemical sciences?

Jeffrey Buter: Speaking for myself, I was quite narrow minded when I started my career in chemistry. There was organic chemistry, and nothing else mattered. While focus is a good thing, being part of the Lipidomic team really opened my eyes which led to a postdoc in the immunology lab of Moody, after my PhD in organic chemistry with Minnaard.

With this experience my advice to a young person is: Keep an open mind during your studies. 九州影院 is everywhere and appreciate its beauty, also when it鈥檚 outside of your favourite chemistry book.

Nicole van der Wel: Never give up. Part of the work we recently published, we have worked on for over a decade, and only now understand. Biology and 九州影院 are complex fields, take your time to understand it.