Liesbet Temmerman

Liesbet Temmerman
KU Leuven | ku leuven · Department of Biology

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50
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Publications

Publications (50)
Article
Full-text available
To find drivers of healthy ageing, a genome-wide association study (GWAS) was performed in healthy and unhealthy older individuals. Healthy individuals were defined as free from cardiovascular disease, stroke, heart failure, major adverse cardiovascular event, diabetes, dementia, cancer, chronic obstructive pulmonary disease (COPD), asthma, rheumat...
Article
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The Q system allows for conditional gene expression in several organisms, including C. elegans. We aimed to apply this system in C. elegans neurons to obtain temporally-resolved, tissue-specific expression of a fluorescent reporter. We report that, in our hands, there is undesired expression of the reporter in conditions where expression is suppose...
Article
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Transcriptome and ribosome sequencing have revealed the existence of many non-canonical transcripts, mainly containing splice variants, ncRNA, sORFs and altORFs. However, identification and characterization of products that may be translated out of these remains a challenge. Addressing this, we here report on 552 non-canonical proteins and splice v...
Article
A mechanistic understanding of biology requires appreciating spatiotemporal aspects of gene expression and its functional implications. Conditional expression allows for (ir)reversibly switching genes on or off, with the potential of spatial and/or temporal control. This provides a valuable complement to the more often used constitutive gene (in)ac...
Article
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Transcription factors govern many of the time-and tissue-specific gene expression events in living organisms. CEH-60, a homolog of the TALE transcription factor PBX in vertebrates, was recently characterized as a new regulator of intestinal lipid mobilization in Caenorhabdi-tis elegans. Because CEH-60's orthologs and paralogs exhibit several other...
Article
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Background: Although several studies demonstrate prion-like properties of Tau fibrils, the effect of size in the seeding capacity of these aggregates is not fully understood. The aim of this study is to characterize Tau seeds by their size and seeding capacity. Methods: Tau aggregates were isolated from postmortem AD brain tissue and separated f...
Article
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Sleep and wakefulness are fundamental behavioral states of which the underlying molecular principles are becoming slowly elucidated. Transitions between these states require the coordination of multiple neurochemical and modulatory systems. In Caenorhabditis elegans sleep occurs during a larval transition stage called lethargus and is induced by so...
Article
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Getting a grip on how we may age healthily is a central interest of biogerontological research. To this end, a number of academic teams developed platforms for life- and healthspan assessment in Caenorhabditis elegans. These are very appealing for medium- to high throughput screens, but a broader implementation is lacking due to many systems relyin...
Article
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The onset of sexual maturity involves dramatic changes in physiology and gene expression in many animals. These include abundant yolk protein production in egg-laying species, an energetically costly process under extensive transcriptional control. Here, we used the model organism Caenorhabditis elegans to provide evidence for the spatiotemporally...
Article
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Metformin is the first-line therapy for treating type 2 diabetes and a promising anti-aging drug. We set out to address the fundamental question of how gut microbes and nutrition, key regulators of host physiology, affect the effects of metformin. Combining two tractable genetic models, the bacterium E. coli and the nematode C. elegans, we develope...
Article
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Numerous neuropeptide systems have been implicated to coordinately control energy homeostasis, both centrally and peripherally. However, the vertebrate neuropeptide Y (NPY) system has emerged as the best described one regarding this biological process. The protostomian ortholog of NPY is neuropeptide F, characterized by an RXRF(Y)amide carboxytermi...
Article
Introduction: Neuropeptides are neuro-endocrine signaling molecules capable of signaling as neurotransmitters, neuromodulators or neurohormones. Studying how neuropeptide signaling is integrated in endocrine signaling pathways and how neuropeptides regulate endogenous processes is crucial to understanding how multicellular organisms respond to envi...
Preprint
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As demonstrated in various animal models, organismal longevity can be achieved via interventions that at the mechanistic level could be considered to entail ‘defensive’ responses: most long-lived mutants focus on somatic maintenance, while reducing growth pathway signalling and protein translation and turnover. We here provide evidence that the opp...
Article
Antioxidants were long predicted to have lifespan-promoting effects, but in general this prediction has not been well supported. While some antioxidants do seem to have a clear effect on longevity, this may not be primarily as a result of their role in the removal of reactive oxygen species, but rather mediated by other mechanisms such as the modul...
Article
Full-text available
Neuropeptides constitute a vast and functionally diverse family of neurochemical signaling molecules, and are widely involved in the regulation of various physiological processes. The nematode C. elegans is well-suited for the study of neuropeptide biochemistry and function, as neuropeptide biosynthesis enzymes are not essential for C. elegans viab...
Article
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BackgroundA series of human diseases are caused by the misfolding and aggregation of specific proteins or peptides into amyloid fibrils; nine of these diseases, referred to as polyglutamine diseases, are associated with proteins carrying an expanded polyglutamine (polyQ) region. While the presence of this latter is thought to be the determinant fac...
Article
In C. elegans research, transcriptional activation of glutathione S-transferase 4 (gst-4) is often used as a read-out for SKN-1 activity. While many heed an assumed non-exclusivity of the GFP reporter signal driven by the gst-4 promoter to SKN-1, this is also often ignored. We here show that gst-4 can also be transcriptionally activated by EOR-1, a...
Article
Full-text available
Human longevity continues to increase world-wide, often accompanied by decreasing birth rates. As a larger fraction of the population thus gets older, the number of people suffering from disease or disability increases dramatically, presenting a major societal challenge. Healthy ageing has therefore been selected by EU policy makers as an important...
Article
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Vitellogenesis or maternal yolk formation is considered critical to the reproduction of egg-laying animals. In invertebrates, however, most of its regulatory genes are still unknown. Via a combined mapping and whole-genome sequencing strategy, we performed a forward genetic screen to isolate novel regulators of yolk production in the nematode model...
Article
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For more than 20 years, reverse pharmacology has been the preeminent strategy to discover the activating ligands of orphan G protein-coupled receptors (GPCRs). The onset of a reverse pharmacology assay is the cloning and subsequent transfection of a GPCR of interest in a cellular expression system. The heterologous expressed receptor is then challe...
Article
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The antiglycemic drug metformin, widely prescribed as first-line treatment of type II diabetes mellitus, has lifespan-extending properties. Precisely how this is achieved remains unclear. Via a quantitative proteomics approach using the model organism Caenorhabditis elegans, we gained molecular understanding of the physiological changes elicited by...
Article
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Bioactive peptides are present in all metazoan species where they orchestrate diverse functions. In the last decade, high-throughput approaches based on mass spectrometry helped the identification of endogenously occurring peptides in different species. We here review biochemical strategies to obtain sequence information of natural (non-tryptic) pe...
Article
Full-text available
Neuropeptidergic signaling is widely adopted by animals for the regulation of physiology and behavior in a rapidly changing environment. The vasopressin/oxytocin neuropeptide family originates from an ancestral peptide precursor in the antecedent of protostomian and deuterostomian animals. In vertebrates, vasopressin and oxytocin have both hormonal...
Article
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Like most organisms, the nematode Caenorhabditis elegans relies heavily on neuropeptidergic signaling. This tiny animal represents a suitable model system to study neuropeptidergic signaling networks with single cell resolution due to the availability of powerful molecular and genetic tools. The availability of the worm's complete genome sequence a...
Article
Vasopressin- and oxytocin-related neuropeptides are key regulators of animal physiology, including water balance and reproduction. Although these neuropeptides also modulate social behavior and cognition in mammals, the mechanism for influencing behavioral plasticity and the evolutionary origin of these effects are not well understood. Here, we pre...
Article
In Caenorhabditis elegans, pdfr-1 encodes three receptors of the secretin receptor family. These G protein-coupled receptors are activated by three neuropeptides, pigment dispersing factors 1a, 1b and 2, which are encoded by pdf-1 and pdf-2. We isolated a PDF receptor loss-of-function allele (lst34) by means of a mutagenesis screen and show that th...
Article
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Hyperglycemia causes diabetic nephropathy, a condition for which there are no specific diagnostic markers thatpredict progression to renal failure. Here we describe a multiplatform metabolomic analysis of urine from individualswith type 2 diabetes, collected before and immediately following experimental hyperglycemia. We used targetednuclear magnet...
Article
The elucidation of the whole genome of the nematode Caenorhabditis elegans allowed for the identification of ortholog genes belonging to the pigment dispersing hormone/factor (PDH/PDF) peptide family. Members of this peptide family are known from crustaceans, insects and nematodes and seem to exist exclusively in ecdysozoans where they play a role...
Article
Many of the diverse functions of neuropeptides are still elusive. As they are ideally suited to modulate traditional signaling, their added actions are not always detectable under standard laboratory conditions. The search for function assignment to peptide encoding genes can therefore greatly benefit from molecular information. Specific molecular...
Article
Full-text available
Gonadotropin-releasing hormone (GnRH) is a critical and central hormone that regulates vertebrate reproduction. The high conservation of GnRH signaling within the chordates (deuterostomians) raises the important question as to whether its appearance might date back prior to the divergence of protostomian and deuterostomian lineages, about 700 milli...
Article
As a consequence of the Earth's axial rotation, organisms display daily recurring rhythms in behavior and biochemical properties, such as hormone titers. The neuronal system controlling such changes is best studied in the fruit fly Drosophila melanogaster. In the nematode worm Caenorhabditis elegans, most homologs of these genes function in the het...
Article
During recent decades, several research teams engaged in unraveling the molecular structure and the physiological significance of pigment dispersing hormone-like peptides, particularly with respect to colour change and biological rhythms. In this review, we first summarise the entire history of pigment dispersing hormone-like peptide research, thus...
Article
Despite the general knowledge and repeated predictions of peptide G protein-coupled receptors following the elucidation of the Caenorhabditis elegans genome in 1998, only a few have been deorphanized so far. This was attributed to the apparent lack of coevolution between (neuro)peptides and their cognate receptors. To resolve this issue, we have us...
Data
Protein identifications (Table 2). List of identified proteins that are differentially expressed 1 h, 4 h, 8 h and/or 24 h after infection with S. aureus. Proteins in bold were also identified after infection with the gram-negative bacterium Aeromonas hydrophila (Bogaerts et al. 2010, ref 29). Protein names in italic represent the human orthologues...
Data
Comparison table (Table 3). Summary of proteins which are found differentially expressed upon challenge with both S. aureus (this paper) and A. hydrophila (Bogaerts et. al 2010, ref 29). "+" is up- and "-" is downregulated at least at one time point of the experiment. Proteins in red show an opposite pattern between the two conditions.
Article
The striking similarities between the innate defences of vertebrates and invertebrates as well as the amenability of Caenorhabditis elegans for genetic analysis, have made this free-living ground nematode a popular model system in the study of bacterial pathogenesis. Although genetic studies have brought new insights, showing the inducibility and p...
Article
Full-text available
The success of invertebrates throughout evolution is an excellent illustration of the efficiency of their defence strategies. Caenorhabditis elegans has proven to be an appropriate model for transcriptome studies of host-pathogen interactions. The aim of this paper is to complement this knowledge by investigating the worm's response to a Staphyloco...
Article
The neuropeptides pigment dispersing factor (PDF) and vasoactive intestinal peptide (VIP) are known as key players in the circadian clock system of insects and mammals, respectively. In this study, we report the discovery and characterization of a widely conserved PDF-like neuropeptide precursor pathway in nematodes. Using a combinatorial approach...
Article
This study addresses the biological function of CG18594, a Drosophila melanogaster phosphatidylethanolamine-binding protein (PEBP) that we named PEBP1, by combining fly genetics, survival experiments and differential proteomics. We demonstrate that transgenic flies overexpressing PEBP1 are highly protected against bacterial infection due to the rel...
Data
Sequences of the 7 Schistocerca gregaria housekeeping genes. The sequences of the identified housekeeping genes are provided in this document. The primer sequences are highlighted in black.
Data
Raw data of the real time PCRs. The data provided represent the calculated average CT values of the locust L5 and adult brain samples. In addition, the data for both developmental conditions are represented in a graph.
Article
Neuromedin U (NMU) in vertebrates is a structurally highly conserved neuropeptide of which highest levels are found in the pituitary and gastrointestinal tract. In Drosophila, two neuropeptide genes encoding pyrokinins (PKs), capability (capa) and hugin, are possible insect homologs of vertebrate NMU. Here, the ligand for an orphan G protein-couple...
Article
Full-text available
To obtain reliable quantitative RT-PCR data, normalization relative to stable housekeeping genes is required. However, in practice, expression levels of 'typical' housekeeping genes have been found to vary between tissues and under different experimental conditions. To date, validation studies of reference genes in insects are extremely rare and ha...
Article
Full-text available
Members of the cholecystokinin (CCK)/gastrin family of peptides, including the arthropod sulfakinins, and their cognate receptors, play an important role in the regulation of feeding behavior and energy homeostasis. Despite many efforts after the discovery of CCK/gastrin immunoreactivity in nematodes 23 yr ago, the identity of these nematode CCK/ga...

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Projects (2)
Archived project
Royalactin is a royal jelly glycoprotein essential for queen differentiation in honeybees. Royalactin plays a central role in this process by switching on the epidermal growth factor (EGF) receptor signaling pathway, which ultimately leads to epigenetic changes and a long-lived queen phenotype. We previously provided the first evidence for its longevity-promoting actions in a non-insect species by studying royalactin-fed Caenorhabditis elegans (Experimental Gerontology 2014). We demonstrated that royalactin requires both Epidermal Growth Factor (EGF, LIN-3) and its receptor (LET-23) for extension of nematode lifespan by ca. 25%. Royalactin also increases oxidative stress tolerance and locomotion in adult nematodes, suggesting a positive effect on healthspan as well. Yet, the mechanism by which royalactin exerts these EGF-mediated effects remained fundamentally unknown. Via an integrative approach using proteomic, biochemical and phenotypic techniques and the model organism C. elegans, we try to gain molecular understanding of the physiological changes elicited by royalactin. Recently we observed that Royalactin might increase global protein translation and proteasome activity, and displays no trade-off regarding reproductive capacity, body size and longevity. This is a rather paradoxical outcome, since longevity is more commonly associated with reduced protein translation. Yet, here we identify and characterize a novel lifespan-extending intervention, where enhanced translation seems to be beneficial for the aging organism. Further work is now being carried out to entangle this complex knot between longevity and protein translation, and assess whether royalactin's effects are also present in other organisms. Ongoing: - Identifying effectors that mediate longevity - Quantifying proteasome activity in vivo - Experiments on human cell lines
Project
http://www.h2020awe.eu/ About us: Ageing with elegans is a project funded by the European Commission under the Horizon 2020 Research and Innovation programme based on a collaboration of thirteen academic research groups and four companies from thirteen EU and three non-EU countries (Switzerland, USA, China). The project started on May 1st 2015 and will run until April 31st 2020. The consortium will validate C. elegans as a healthspan model for better understanding of the factors responsible for healthy ageing, and will develop evidence-based prevention, diagnostic, and therapeutic strategies. Problem statement: Healthspan (the life period when one is generally healthy and free from serious disease) depends on nature (genetic make-up) and nurture (environmental influences, from the earliest stages of development throughout life). Genetic studies increasingly reveal mutations and polymorphisms that may affect healthspan. Similarly, claims abound about lifestyle modifications or treatments improving healthspan. In both cases, rigorous testing is hampered by the long lifespan of model organisms like mice (let alone humans) and the difficulty of introducing genetic changes to examine the phenotype of the altered genome. Solution: This project will develop C. elegans as a healthspan model. Already validated extensively as an ageing model, this organism can be readily modified genetically, and effects of environmental manipulations on healthspan can be measured in days or weeks. Once validated as a healthspan model, it can be used for an initial assessment of preventive and therapeutic measures for humans, as well as for risk identification and the initial evaluation of potential biomarkers. It will also prove useful to study interactions between genetic and various environmental factors. Approach: A high-throughput assay for healthspan in C. elegans will be used to conduct a genome-wide RNAi screen for genes affecting healthspan. These genes will be compared with the ones showing under- or over-represented polymorphisms in cohorts of elderly persons who aged exceptionally well. Moreover, the molecular targets of Chinese medicinal plants that increase healthspan in C. elegans as well as in mice will be elucidated. From these combined human, C. elegans and mouse data, biochemical pathways affecting healthspan will be derived using (amongst others) advanced data mining methods. This project has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 633589.