GENiE RESEARCH

C. elegans as experimental model to investigate in vivo the molecular mechanisms underlying the aggregation of amyloidogenic proteins

We investigate the molecular events underlying in vivo amyloidogenesis correlating the phenotype of the transgene with the disease insurgence, the degeneration, the protein expression and its aggregation. Different transgenic strains expressing various fragments of human amyloidogenic proteins responsible for central and systemic amyloidosis are available in our lab and are currently used to study.

This multidisciplinary genomic and molecular integrated approach give us the opportunity to obtain information on the molecular functions of genes related to amyloidosis and for the development of innovative therapeutic strategies.

(L Diomede lab)

What is ageing and can we prevent it from happening?

We all know how the human body gradually changes over time; we get wrinkles, our hair turns gray, our joints become stiff, our muscles get weaker…a process known to us as ageing. Yet, biologists still do not understand the molecular mechanisms of this slow process. Is it damage accumulation, a gradual failure of genetic programs, or anything we didn’t think of yet? We use the nematode C. elegans in our ageing research because this organism ages, just like we do, but at much faster rate. With a lifespan of only two to three weeks, a superior genetic amenability and no major ethical issues, we hope that this tiny, 1-mm animal will allow fast progress in the field of ageing research.
(B Braeckman lab)

Modifiers of age-related protein aggregation and toxicity

We use C. elegans to understand the link between aging and dementia. We focus on the role of aggregation-prone proteins that are thought to play a major role in disease. How they play a role is only poorly understood. With C. elegans we have indentified genes that drive the aggregation and toxicity of disease proteins. Without these genes the worms are protected against their damaging effect. We are working out the role of these genes in development and aging and translate our findings to human cells andmice. Our research provides a basic understanding of how cells and organisms cope with damaged proteins during aging and will explain why evolution has conserved genes that at old age accelerate disease.
(E Nollen lab)

Understanding how organisms respond to DNA damage

DNA damage such as that induced by solar UV irradiation poses a serious threat to the integrity and proper functioning of the genome. Cells are equipped with a complex network of DNA repair and signaling pathways, called the DNA damage response, to protect against and repair DNA damage. C. elegans is an excellent model organism to study the impact of DNA damage on health, growth and development due to its well-known biology, small size and short generation time. Furthermore, due to its transparency, we are able to use microscopy on living worms to study how the DNA damage response is differentially organized in vivo, i.e. in different cell types and throughout development.

(W Lans lab)

Don’t get too excited: K2P Potassium channels and the regulation of the membrane potential

Electrical polarization of the cell membrane is a universal feature of nearly all eukaryotic cells. Potassium-selective ion channels play a central role in the establishment and the maintenance of these electrical gradients, which allow the flow of information in the nervous system but also serve as a source of energy for the cell. Our work is focused on understanding the molecular and cellular components that regulate the function of C. elegans K2P potassium channels.
Despite their basic role and broad conservation, comparatively little is known about the genes and cellular processes that control their function in vivo. In particular, we are interested in identifying factors that regulate the number, the activity and the distribution of K2P channels at the cell surface.

(T. Boulin lab)

An elegans approach for biological research, or The most elegant approach for biological research

C. elegans is a free-living nematode of ~1 mm in length with a short generation cycle (~3 days) and lifespan (~3 weeks). This constant replenishment represents a practically infinite source of animals for experimentation and enables researchers to rapidly conduct large genetic and pharmacological screens, processes that would require significantly more time, labor, and resources in a mammalian system. In addition, hundreds of animals may be analyzed for each data point, a clear statistical advantage in comparison with other models in which such sample sizes are impossible. Moreover, its transparent body allows the visualization of cell types at all stages of development and aging.
(E Dalfo lab)

The genome in three dimensions

The entire genetic information of an organism is packaged in a tiny nucleus in each of its cells. How does this packaging influence gene activity, and hence cellular function? To what extent does it change during development of the organism? These are the main questions we are trying to answer using C. elegans as a model organism. Thanks to its many features (compact genome, reproducible development, ease of imaging, etc.), the worm can help us to determine whether there exists an additional level of information in the 3D structure of the genome.

(C. Lanctot lab)

Epigenetic control of development

The normal development of an organism depends on factors that instruct cells to develop into the various cell and tissue types forming the body. Transcription factors and chromatin modifiers are very important players in these programming and reprogramming events. Our lab chose to investigate the function of chromatin remodelers during development focusing on LET-418/Mi-2. This epigenetic regulator is required for normal development of the worm. Using biochemical and genetic approaches, we found that LET-418/Mi-2 interacts with other chromatin factors, to form a network of proteins that regulates development, cell fate, organogenesis and ageing.

(C. Wicky lab)

Worms smell and taste just like humans

We use the nose of C. elegans to study nervous system development per se and as it relates to humans. To survive in a complex environment, one needs to pick up its cues (sensory information like smelling, tasting, etc.), compute and integrate that information and then react to it appropriately. One needs a highly diversified and powerful nervous system information network that can do all this: sensory neurons (input), higher order brain structures (computation) and motorneurons (output) that control muscle action. In this regard worms and humans are very much alike. They use a very similar arrangement of neurons and set of proteins in these neurons to properly manage sensory information.

(P Swoboda lab)

Cellular processes that control protein synthesis in stress, aging and disease

Our research focuses on the role of evolutionary conserved cellular processes, which control protein synthesis rates at the level of translation and metabolism of mRNAs, in survival and lifespan of C. elegans. We investigate the impact and the interplay of major nutrient-sensing signaling pathways (GCN-2, TOR) in longevity and stress response. We also study the pattern and function of specific RNA granules that dictate mRNA lives in the cytoplasm, such as P-bodies (PBs) and stress granules (SGs), during aging, stress and pathogenesis of neurodegenerative diseases.

Our work provides new insights into key aging modulators and may contribute in treating age-related dysfunction/degeneration.

(P. Syntichaki lab)

Cell polarity – shaping the structure and functioning of animal cells and tissues

An essential property of animal cells is the presence of an axis of polarity, which is needed for their proper functioning. For example, intestinal cells absorb nutrients on the apical side, and pass these along to the blood stream on the basal side. Cell polarity is also critical for asymmetric cell divisions where the daughters take different fates, such as stem cell divisions. Finally, cell polarity is essential for the structural organization of epithelia, and loss of epithelial organization is thought to contribute to the development of cancer. In C. elegans, polarity establishment can be followed live in individual cells, and past studies have already greatly contributed to our understanding of cell polarity.

(M. Boxem lab)