About
34
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Introduction
Current institution
Additional affiliations
November 2015 - present
July 2011 - October 2015
Position
- PhD Student
Description
- To address fundamental questions concerning drug-induced mitochondrial dysfunction, Caenorhabditis elegans is applied as a model organism. The project aims at (i) dissecting the molecular mechanism underlying drug-induced mitochondrial dysfunction.
Publications
Publications (34)
Deregulated energy homeostasis represents a hallmark of aging and results from complex gene-by-environment interactions. Here, we discovered that reducing the expression of the gene ech-6 encoding enoyl-CoA hydratase remitted fat diet-induced deleterious effects on lifespan in Caenorhabditis elegans , while a basal expression of ech-6 was important...
Caenorhabditis elegans is a highly versatile model system, intensively used for functional, genetic, cytometric, and integrative studies. Due to its simplicity and large muscle cell number, C. elegans has frequently been used to study mitochondrial deficiencies caused by disease or drug toxicity. Here we describe a robust and efficient method to vi...
Comprehensive metabolomic and lipidomic mass spectrometry methods are in increasing demand; for instance, in research related to nutrition and aging. The nematode Caenorhabditis elegans is a key model organism in these fields, owing to the large repository of available C. elegans mutants and their convenient natural lifespan. Here, we describe a ro...
Deregulated energy homeostasis represents a hallmark of aging and results from complex gene-by-environment interactions. Here, we discovered that reducing the expression of the gene ech-6 encoding enoyl-CoA hydratase remitted fat diet-induced deleterious effects on lifespan in Caenorhabditis elegans , while a basal expression of ech-6 was important...
Comprehensive metabolomic and lipidomic mass spectrometry methods are in increasing demand, for instance in research related to nutrition and aging. The nematode C. elegans is a key model organism in these fields, due to the large repository of available C. elegans mutants and their convenient natural lifespan. Here, we describe a robust and sensit...
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...
Microarray datasets of genes that are differentially expressed between daf-2 mutant and N2 worms or between eat-2 mutant and N2 worms.
Metabolite profiles of daf-2 mutant, eat-2 mutant and N2 worms.
Impaired insulin/IGF-1 signaling (IIS) and caloric restriction (CR) prolong lifespan in the nematode C. elegans. However, a cross comparison of these longevity pathways using a multi-omics integration approach is lacking. In this study, we aimed to identify key pathways and metabolite fingerprints of longevity that are shared between IIS and CR wor...
The ability to efficiently adapt metabolism by substrate sensing, trafficking, storage and utilization, dependent on availability and requirement is known as metabolic flexibility. In this review, we discuss the breadth and depth of metabolic flexibility and its impact on health and disease. Metabolic flexibility is essential to maintain energy hom...
Impaired insulin/IGF-1 signaling (IIS) pathway and caloric restriction (CR) are two well-established interventions to prolong lifespan in worm C. elegans . However, a cross comparison of these longevity pathways using a multi-omics integration approach is lacking. In this study, we aimed to identify key pathways and metabolite fingerprints of longe...
Use of some HIV-1 nucleoside reverse transcriptase inhibitors (NRTI) is associated with severe adverse events. However, the exact mechanisms behind their toxicity has not been fully understood. Mitochondrial dysfunction after chronic exposure to specific NRTIs has predominantly been assigned to mitochondrial polymerase-γ inhibition by NRTIs. Howeve...
NRTIs pre-exposure protected against subsequent paraquat exposure.
4mM paraquat (PQ) survival assay of NRTI exposed animals. Statistics were calculated by two sided student’s t-test assuming unequal variance, compared to the control of that same time point (72h of PQ exposure).
(TIF)
Supplementation of NAC does not affect movement.
The number of sigmoidal body bends per worm per minute can be used as a proxy for fitness. Anti-oxidant concentration = 100μM. Statistics were calculated by two sided student’s t-test assuming unequal variance compared to control of that same time point. n.s. = not significant.
(DOCX)
H2O2 and paraquat do not influence OCR.
Immediate OCR rates after injection of H2O2 and paraquat (PQ) do not change. The lack of these pro-oxidants to have an immediate effect on OCR supports the observations that they do not directly inhibit MRC complex function at the concentrations used in this study [53,54].
(TIF)
NAC does not alter ATP levels.
ATP levels did not change upon exposure to 500μM NAC. In vivo ATP levels measured after 2 minutes of exposure.
(TIF)
AZT portrays a biphasic dose response in C. elegans.
In accordance with mitohormetic events triggered by inhibited MRC function and an increase in ROS, 200μM AZT caused significant lifespan extension in C. elegans. An increase in AZT concentration above 200μM steadily decreased life span in L4 animals, indicating that NRTIs cause a biphasic dose re...
NRTIs likely did not cause lifespan extension through caloric restriction.
In C. elegans, caloric restriction during development or adulthood can cause lifespan extension by increasing mitochondrial activity and prompting the expression of genes involved in stress resistance and longevity [95]. Although pharyngeal pumping is not a direct measure of...
NAC decreased mtDNA replication associated with development.
NAC reduced the normal mtDNA copy number increase during 1h exposure. 100μM NAC decrease mtDNA copy number compared to control nematodes after 1h exposure (dark grey vs 1h control). mtDNA copy number increases during nematode development and therefore rises (control 0h vs control 1h). Err...
Sodium azide and potassium cyanide reduced ATP production.
Complex IV inhibitors, sodium azide (NaN3) and potassium cyanide (KCn), reduced ATP production. 1mM NaN3 and 50mM KCn reduced in vivo ATP levels measured after 2 minutes of exposure. Statistics were calculated with a two-way ANOVA with replication, compared to the control. * = P<0.05, *** =...
The biological mechanisms of aging have been studied in depth and prominent findings in this field promote the development of new therapies for age-associated disorders. Various model organisms are used for research on aging; among these, the nematode Caenorhabditis elegans has been widely used and has provided valuable knowledge in determining the...
Abnormal nutrient metabolism is a hallmark of aging, and the underlying genetic and nutritional framework is rapidly being uncovered, particularly using C. elegans as a model. However, the direct metabolic consequences of perturbations in life history of C. elegans remain to be clarified. Based on recent advances in the metabolomics field, we optim...
Today HIV-1 infection is recognized as a chronic disease with obligatory lifelong treatment to keep viral titers below detectable levels. The continuous intake of antiretroviral drugs however, leads to severe and even life-threatening side effects, supposedly by the deleterious impact of nucleoside-analogue type compounds on the functioning of the...
Caenorhabditis elegans is a highly malleable model system, intensively used for functional, genetic, cytometric, and integrative studies. Due to its simplicity and large muscle cell number, C. elegans has frequently been used to study mitochondrial deficiencies caused by disease or drug toxicity. Here, we describe a robust and efficient method to v...
Aging is a universal biological process that afflicts every creature on this planet. To date, we have a very poor understanding of what actually causes this degeneration. A commonly held view is that aging is the result of damage accumulation over a lifetime. However, research has shown that aging is not only the result of wear and tear in the orga...
Highly active antiretroviral therapy (HAART) has significantly increased life expectancy of the human immunodeficiency virus (HIV)-positive population. Nevertheless, the average lifespan of HIV-patients remains shorter compared to uninfected individuals. Immunosenescence, a current explanation for this difference invokes heavily on viral stimulus d...
Development and acclimation processes to the environment are associated with large-scale changes in chromatin compaction in Arabidopsis (Arabidopsis thaliana). Here, we studied the effects of light signals on chromatin organization. A decrease in light intensity induces a large-scale reduction in chromatin compaction. This low light response is rev...
