Biology subjects

Timmerman, E.

Publications and source records attributed to Timmerman, E..

5 recordsLinked to original sources

bioRxiv2026

Role of the gut microbiota in the remodelling of the jejunal, colonic, hepatic and blood proteomes in a mouse model of Anorexia Nervosa

Background: Anorexia nervosa (AN) is a typical form of eating disorder characterized by a severe body weight loss, a fear of gaining weight and dysmorphophobia. This disorder is associated with both psychiatric comorbidities and multi-organ dysfunctions. Increasing evidence suggests a role of the gut microbiota in the onset or maintenance of AN. Although a dysbiosis has been reported in patients with AN, the physiological consequences of this dysbiosis remain poorly documented. To gain further insight into the role of the gut microbiota in the pathophysiology of AN, we used the murine Activity-based Anorexia (ABA) model and compared the remodelling of the jejunal, colonic, hepatic and blood proteomes occurring in male mice with intact gut microbiota, as well as in gut microbiota-depleted animals. Results: We observed a significant proteome remodelling in several organs in response to the ABA model. More than 250 proteins involved in energy metabolism, catabolic processes, lipid metabolism, ghrelin regulation, and immune functions were found to show altered abundance in ABA mice compared to control mice. We observed in addition in the blood of ABA mice a significant increase in the level of circulating proteasome. By comparing mice treated or not with antibiotics, we identified 75 proteins whose regulation in ABA mice is gut-microbiota dependent. The other identified proteins were similarly affected in ABA mice with intact or depleted gut microbiota, suggesting that these factors are mainly regulated by food starvation and physical activity, and not directly by the gut microbiota. We finally confirmed that ORM2, a protein identified as significantly decreased in the plasma of ABA mice, is also decreased in the blood of patients suffering from AN. Conclusion: Our results demonstrate that the Activity-Based Anorexia model is associated with an extensive proteome remodelling in several organs and tissues. We highlight in addition that some of these targets are regulated in a gut microbiota-dependent manner, thereby reinforcing the hypothesis of a role of the gut microbiota in Anorexia Nervosa. Together, our study provides a valuable resource to better delineate the impact of undernutrition and maladaptive physical activity on the proteome of various organs and the role of the gut bacteria in the pathophysiology of Anorexia Nervosa.

pathology↗

bioRxiv2026

Organ identity shapes autophagy dynamics and selectivity in plants

Plants, with their unique evolutionary trajectory and complex physiological adaptations, have developed organ-specific mechanisms to cope with various environmental stresses. Autophagy, an essential catabolic process, plays an important role in maintaining plant growth, immunity, and overall fitness. In this study, we reveal the spatio-temporal dynamics of autophagic responses in Arabidopsis thaliana roots and shoots under different stress conditions, including AZD8055 treatment and carbon and nitrogen depletion. Our findings demonstrate that roots exhibit stronger autophagic activity than shoots under all three conditions, highlighting the unique adaptations of these two organs. Furthermore, we dissect the selectivity of autophagy in targeting organelles, revealing immediate, delayed, and no uptake categories. Additionally, we observe organelles coexisting within autophagic bodies, shedding light on the complexity of cargo selection. This study enhances our understanding of plant specific autophagy dynamics, emphasizing its role in sustaining the source-sink functions and offering insights into plant adaptation to diverse stressors.

plant biology↗

bioRxiv2026

A novel nanobody-based approach for targeting heterogeneous Acinetobacter baumannii isolates and closely related pathogenic Acinetobacter spp.

Acinetobacter baumannii is a top-priority, ESKAPE pathogen that poses a major challenge to human health. The pathogen is difficult to combat due to its extensive arsenal of antibiotic resistance and its protective polysaccharide capsule. In addition, A. baumannii isolates are highly heterogeneous, which complicates the development of rapid detection methods or novel targeted therapeutic approaches. Here, we discovered and characterized a new biotechnological tool, the nanobody H7 (NbH7), along with its conserved target, the surface-exposed Omp25 protein of A. baumannii, and elucidated their interaction at the molecular level. Moreover, we demonstrate that NbH7-functionalized magnetic beads enable selective and efficient capture of A. baumannii from bacterial mixtures, including non-pathogenic intestinal bacteria. This provides proof of concept for a new targeting system that remains effective across diverse A. baumannii clinical isolates and capsule types and holds potential for use in diagnostic cell enrichment and targeted therapies.

molecular biology↗

bioRxiv2024

High-throughput nano-flow proteomics using a dual-column electrospray source

With current trends in proteomics, especially regarding clinical and low input (to single cell) samples, it is increasingly important to both maximize the throughput of the analysis and maintain as much sensitivity as possible. The new generation of mass spectrometers (MS) are taking a huge leap in sensitivity, allowing to analyze samples with shorter liquid chromatography (LC) methods while digging as deep in the proteome. However, the throughput can be doubled by implementing a dual column nano-LC-MS configuration. For this purpose, we used a dual-column setup with a two-outlet electrospray source, and compared it to a classic dual-column setup with a single-outlet source.

biochemistry↗

bioRxiv2023

Structure-function analysis of a calcium-independent metacaspase reveals a novel proteolytic pathway for lateral root emergence

Metacaspases are part of an evolutionarily broad family of multifunctional cysteine proteases, involved in disease and normal development. Despite the extensive study of metacaspases in the two decades since their discovery, the structure-function relationship of metacaspases remains poorly understood. Furthermore, previous studies on their function have been thwarted by the redundancy in gene copy number and potential phenotypic suppression of genetic mutations, especially in plants. Here, we have solved the X-ray crystal structure of an Arabidopsis thaliana type II metacaspase (AtMCA-IIf) that belongs to a particular sub-group that does not require calcium ions for activation. Compared to crystal structures of other metacaspases and caspases, the AtMCA-IIf active site is structurally similar and poses a conundrum for the catalytic mechanism of the cysteine-histidine dyad. To study metacaspase activity in plants, we developed an in vitro chemical screen to identify small molecule metacaspase inhibitors. Several hits with a minimal thioxodihydropyrimidine-dione (TDP) structure were identified, some being specific inhibitors of AtMCA-IIf. We provide a mechanistic basis for inhibition by the TDP-containing compounds through molecular docking onto the AtMCA-IIf crystal structure. Finally, a TDP-containing compound (TDP6) was effective at inhibiting lateral root emergence in vivo, likely through the inhibition of metacaspases that are specifically expressed in the endodermal cells overlaying developing lateral root primordia. In the future, the small compound inhibitors and crystal structure of AtMCA-IIf can be used to study metacaspases in various other species, such as important human pathogens including those causing neglected diseases.

plant biology↗