The Lipidomics Team studies lipid molecules with the aim of developing reliable diagnostic tests and effective vaccines against tuberculosis and other infectious diseases. Thanks to their innovative research, this group has gained insight into how tuberculosis bacteria survive in the human body, using a clever trick to bypass the immune system. Insights gained here are expected to help map other important bacterial pathogens.
The fight against tuberculosis and other bacterial infectious diseases
Tuberculosis is the world’s deadliest bacterial infectious disease. Every year, more than one and a half million people die from the disease and some ten million new cases of infection are diagnosed. A major difficulty in the fight against tuberculosis is diagnosis. Existing tests are not reliable enough and too expensive for the countries where they are most needed. In addition, there is still no effective tuberculosis vaccine that provides long-term protection against open pulmonary tuberculosis in adolescents and adults, even though this is the main form of transmissible tuberculosis.
The Lipidomics Team at the University of Groningen has been working for twenty years to develop fundamental methods for combating bacterial infectious diseases such as tuberculosis. Their research focuses on the human immune system, within which specialised cells and proteins work together to protect the body from pathogens such as bacteria. What sets the team apart is their willingness to step outside the box. For instance, the dominant thinking for a long time was that proteins play the main role in the defense response of the human immune system. From the beginning, however, the Lipidomics Team has focused on so-called ‘lipids’. Lipids come in many shapes and sizes. It is an umbrella term for fat-like substances that play an important role in all kinds of processes in the human body. The team showed that even the most thoroughly studied bacteria still contain many unknown lipids, despite the crucial role these molecules play in the human immune response. This highly original insight combined with their revolutionary approach has led to numerous groundbreaking discoveries in recent decades.
"Lipids play a crucial role in the human immune response"
For example, a key fundamental question was why tuberculosis bacteria can survive in the human body. The team discovered that these bacteria bypass the immune system by producing unique lipids. In a nutshell: when pathogenic bacteria enter the body, they are attacked by white blood cells, which absorb the bacteria into their ‘stomach’ after which acidity is reduced to kill the bacteria. However, tuberculosis bacteria manage to avoid this acidification by creating a kind of stomach acid inhibitor with the production of lipids. In this way, the bacteria can remain dormant in the body for a long time until the immune system is weakened, and the carrier becomes ill.
The Lipidomics Team uniquely brings together expertise in organic chemistry, microbiology and immunology. It starts by detecting new lipids. These are discovered by comparing pathogenic and non-pathogenic bacteria. These lipids are then chemically replicated in the laboratory. Then the interaction between the counterfeited ‘pure’ lipids and the human immune system is studied. For the first time ever, this innovative method made it possible to largely identify the vast array of lipids in disease-causing bacteria, and especially those lipids involved in causing disease. These findings transformed the scientific understanding of tuberculosis infectivity and gave The Lipidomics Team a leading position in global collaborations.
"Every year, more than one and a half million people die from tuberculosis and there is still no effective vaccine"
In addition to their research work, the group has established a lipid bank that will likely prove to be of great importance for future breakthroughs in this area of science. The group has now made some 100 chemically replicated lipid molecules available to the entire research community. Their own mission in this field is clear: to establish a reliable diagnostic test and develop an effective vaccine for tuberculosis. Both are now in development, although it will take several years before they reach the market.
The leads for new research are numerous. In the coming years, the team hopes to further expand its knowledge of bacterial lipids. Their method is expected to be useful for mapping other important bacterial pathogens besides tuberculosis. As a next step, the team therefore plans to set up an innovative research programme on newly discoverable lipids in the bacteria that cause typhoid fever, blood poisoning and skin infections. Their main questions are: how can these bacteria make us so terribly ill and what role do lipids play in this?
Adriaan J. Minnaard (1968) studied Molecular Sciences at Wageningen Agricultural University, where he obtained his PhD in Organic Chemistry in 1997. Since 1999, he has been working at the Stratingh Institute of Chemistry at the University of Groningen. His research group develops methods for the synthesis of complex molecules, including those from M. tuberculosis. This work is supported by NWO, the National Institute of Health, ARC CBBC and the Carbohydrate Competence Center. Together with Moody and Van Rhijn, Minnaard received an NWO Team Science Award in 2020.
scientist who trained at the Johns Hopkins School of Medicine and serves as Professor of Medicine at Harvard Medical School. His laboratory studies the human immune response to major bacterial pathogens, such as M. tuberculosis, as well as T cell activation in autoimmune diseases. His team developed lipidomics platforms for the discovery of lipids in pathogenic bacteria and lipid antigens presented to T cells by CD1 proteins. This work was supported by the Pew Foundation, the Wellcome Trust, the Mitzutani Foundation, the Bill and Melinda Gates Foundation, the Burroughs Wellcome Foundation, the MRC, the NWO and the NIH.
Ildiko van Rhijn (1968) studied Biology and violin in Amsterdam and received her PhD in Immunology at the University of Utrecht in 2002. Her research groups and academic appointments are in Utrecht (the Faculty of Veterinary Medicine) as well as in Boston (Brigham and Women’s Hospital and Harvard Medical School). The focus of her research is the discovery of new targets of the immune system, which has led to the identification of unusual bacterial compounds that stimulate T cells. Van Rhijn received an NWO Team Science Award in 2020, together with Minnaard and Moody.
