Het proefschrift omschrijft de chemische synthese van fenolische glycolipiden van verschillende mycobacteriën met het doel om deze te kunnen gebruiken voor immunologisch onderzoek.

New drugs for use as tuberculosis (TB) treatment are needed due to the constrains of classical antibiotics against TB and the rise of antibiotic-resistant strains, making TB a harder and harder disease to treat.

Though tuberculosis can be cured today, new resistant strains of the bacteria are becoming a growing problem in the medical world. Biologist Annemarie Meijer and her colleagues are studying resistance to this disease. Their research is already yielding several interesting clues that could help the development…

The research described in this Thesis was aimed at designing and synthesizing nature-inspired compounds as part of TB vaccine discovery.

Tuberculosis (TB) is associated with 1.5 million deaths annually. There is a need exists to optimize both current as well as novel antibiotic combination treatment strategies to improve the effectiveness and safety of treatments against TB.

About nine million people worldwide contract tuberculosis each year. Research into new treatment for this disease has received fresh stimulus with more efficient techniques and a new understanding of how the tuberculosis bacteria works.

Can drug screening for tuberculosis treatment be made more efficient?

Who benefits from CXCR/CXCL chemokine signaling during infection: host or pathogen?

Can drugs that target host signaling pathways be used to eradicate antibiotic-resistant bacteria?

The infectious diseases malaria and tuberculosis are responsible for 2.1 million deaths every year. Leiden researchers are currently testing a new tuberculosis vaccine.

Effective host defence against tuberculosis bacteria depends on a properly balanced level of inflammation. The Inflammafish project uses zebrafish larvae to study how autophagy controls this inflammation and vice versa.

In this thesis, I study 1) metabolic alterations in tuberculosis related to wasting syndrome in human patients as well as in rodent and fish animal models. 2) effects of the mutation of the leptin gene on cachexia and diabetes in rodent and zebrafish animal models.

Mycobacterium tuberculosis (Mtb), the pathogen causing tuberculosis (TB), is the leader among all pathogens responsible for the most human deaths today and it is considered as one of the top 10 causes of death worldwide. There is an increasing occurrence of multidrug-resistant and even totally drug-resistant…

Can we exploit the cell death machinery of the host to develop new host-directed anti-TB treatments?

What is the role of cell wall-deficiency in the persistence of tuberculosis?

Tuberculosis (TB) is a major global health problem caused by the bacterium Mycobacterium tuberculosis (Mtb). In 2015, there were estimated to be 10.4 million new cases and 1.8 million deaths ascribed to TB, making it one of the top 10 causes of death worldwide. Unfortunately, the only current registered…

Are Weyl particles the ideal conductors? Do cells without a cell wall play a role in chronic Tuberculosis infections? Carlo Beenakker and Dennis Claessen want to answer these questions. They both received a KLEIN grant from the NWO. With these grants, NWO wants to stimulate innovative, fundamental r…

IBL-researcher Phil Elks in the group of Annemarie Meijer won the Cell Observatory Publication of the Year 2013. He received the award for his paper in PLoS Pathogens, showing that activation of hypoxia signaling protects against mycobacterial infection.

The cellular recycling system in zebrafish is capable of eating harmful bacteria and thus resist infections such as tuberculosis and salmonellosis. That is written by Leiden biologists from the group of Annemarie Meijer. Stimulating this form of defence could be used in new treatment methods against…

Michiel van der Vaart with a team from Leiden University and the LUMC, led by IBL-researcher Annemarie Meijer, discovered that DRAM1 is a protein that regulates anti-bacterial autophagy, a defense mechanism against infections such as tuberculosis.

This thesis describes the structural and biochemical characterization of the β-lactamase BlaC from Mycobacterium tuberculosis (Mtb), and the Alr and YlmE proteins from Streptomyces coelicolor A3(2).Mtb is the main cause of tuberculosis.

The effective treatment of tuberculosis (TB) remains a major challenge to global health.

Macrophages – the front line of our immune system – protect us from infections. But in the case of the tuberculosis bacteria, this often goes wrong. The group of Annemarie Meijer from the Leiden Institute of Biology has now discovered that macrophages in zebrafish are better able to eliminate tuberculosis…

Promotor: H.P. Spaink, A.H. Meijer Co-promotor: R. Marin-Juez

Autophagy is a fundamental degradative process, maintaining cellular homeostasis and functions in host defense against intracellular pathogens, including mycobacteria and Salmonella.

How is inflammation in tuberculosis controlled by interplay between autophagy and inflammasome signalling?

BlaC is the β-lactamase of Mycobacterium tuberculosis. We show that it can recover from inhibition by clavulanic acid and that phosphate helps it do so.

The function of TLRs in innate immunity has aroused worldwide attention soon after its discovery. Because of the broad functions of TLR2 in innate immunity, the drive for the development of TLR2-targeted vaccines or therapeutic treatments has accelerated in the last decades.

Can we enhance the capacity of host immune cells to kill mycobacteria via production of reactive nitrogen species?

Promotores: A.H. Meijer, H.P. Spaink

In this thesis, bioorthogonal chemistry is combined with correlative light-electron microscopy to selectively label and study pathogenic intracellular bacteria within the host immune cell.

How do mycobacteria subvert the defenses of host immune cells?

How can zebrafish research help understanding human diseases?

TRANSAUTOPHAGY is a European COST action to promote multidisciplinary research on autophagy and translation of knowledge to applications.

The research described in this thesis has, using the zebrafish as a model system, shed new light on the intricate relationship between TB and DM2, in particular on the role of leptin, SHP-1 and glucocorticoids.

PhD defence

The Translational Immuno-Pharmacology group works on translating the efficacy of anti-infective therapy from preclinical (e.g. in vivo) to clinical, and is led by Rob van Wijk. Infectious diseases, such as tuberculosis, are in constant need of new therapies that work better, faster, and with less risk…

An international consortium of research groups is aiming to develop novel antibiotics against the tuberculosis bacteria and two other deadly bacteria. The European Union has awarded a total of 18 million euros to the RespiriTB and RespiriNTM projects. Researchers from the Leiden University Medical Centre…

Can we find and commercialise new treatments for chronic disease that affect our ageing population? And how can we customise this research and development programme to the small but highly-developed Netherlands research economy?

PhD defence

How can zebrafish models be used to gain a better understanding of host-pathogen interaction mechanisms and to screen new drugs for infectious disease treatment?

Tuberculosis causes 1.5 million deaths yearly and anti-tuberculosis therapies are threatened by emergence of drug resistance. Development of innovative drug combinations should be accelerated with the use of translational pharmacological models. Moreover, host-directed therapies (HDT), which stimulate…

β-Lactamases are enzymes that can break down β-lactam substrates, such as antibiotics, preventing the use of these antibiotics for the treatment of various infectious diseases. However, some compounds, β-lactamase inhibitors, can block these enzymes allowing for possible treatments using a combination…

Tuberculosis is an infectious disease which is spreaded through the air. It is caused by Mycobacterium tuberculosis and it led 1.7 million people to death in 2016. This mortarlity rate is concentrated in developing countries such as Indonesia, Philippines, Pakistan, and South Africa. These numbers make…

PhD defence

How can novel bioimaging technologies and vertebrate model species be used to gain a better understanding of early cellular behaviours with the ultimate goal to increase our understanding of human development and disease processes?