Loss of hair cells (HC), the mechanoreceptors of sensory epithelia of the inner ear, is the major cause of non-syndromic hearing disorders. These sophisticated cells are highly sensitive to several otoxic factors including antibiotics, noise or simply ageing because we are born with a finite stock of them. Unlike mammals, lower vertebrates regenerate very efficiently those mechanoreceptors throughout their lifetime. In amphibians and fish, HC are also found in a skin deep sensory organ system, called the lateral line (LL). Organization, physiology, structure, ultra-structure and even gene expression in the LL and sensory epithelia of the inner ear are highly comparable. The LL is constituted of stereotypically distributed sensory patches called neuromasts (N). When HC in the N are destroyed, surrounding support cells (SC) dedifferentiate and a subset of them actively divide and give rise to new HC and SC therefore constituting a steady pool of HC progenitors. Regulation of SC proliferation has been described as controlled by canonical Wnt-signaling mostly based on chemical manipulation. No direct genetic evidence has been provided yet, most probably because of Wnt-signaling involvement in several crucial developmental events rendering mutations in any players of the pathway early lethal. We have previously described a novel and uncharacterized gene which expression we have trapped in a stable transgenic zebrafish line. We showed that it was strictly restricted to SC of the LL and of the olfactory epithelium, another regenerating structure. The cloned sequence revealed a highly-conserved signature domain, the tankyrase 1 binding domain, which lead us to postulate that this gene was a putative homolog of Tankyrase 1 binding protein 1(Tnks1bp1). In cell culture, tankyrase 1 (TNKS1) had been implicated in telomeres length maintenance and mitosis regulation providing a tantalizing mechanistic link. More recently TNKS1 has been described as a new partner of the Wnt-canonical signaling pathway rendering the involvement of tnks1bp1 in HC regeneration even more probable. Using CRISPR-Cas genome editing technology, we generated several null alleles which we started to analyze. The overall development of the LL in tnks1bp1 homozygotes (tnks1bp1-/-) seems unaffected, but as early as 5day post fertilization (dpf) all N have strikingly less HC and SC, which strongly suggests that tnks1pb1 is crucial in maintenance of the HC progenitor pool.

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Chromosome ‘linearity’ is so universal among eukaryotes that we assume it to be evolutionarily advantageous. Nonetheless, formidable challenges are presented by linear chromosome ends, as their resemblance to damage-induced DNA breaks makes them vulnerable to degradation and end-joining pathways that provoke aging or cancer. Julie Cooper’s laboratory studies how telomeres protect chromosome integrity, as well as alternative strategies for chromosome end protection in the absence of canonical telomeres. The lab has also discovered unanticipated roles of telomeres in controlling both spindle and centromere assembly during meiosis. These studies are prompting a re-examination of the roles played by specific microenvironments within the nucleus

Areas of Expertise

https://irp.nih.gov/pi/julia-cooper

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           Proteins from the Bcl-2 family preside over what is essentially the “point-of-no-return” in apoptosis. Pro-apoptotic members of the family promote outer mitochondrial membrane permeabilization and cell death, while anti-apoptotic members promote cell survival by blocking their pro-apoptotic counterparts. The complexity of the process is compounded due to the different conformations each of the proteins can adopt, as well as by the important role played by the lipids in mediating protein-protein interactions. We use reconstituted membrane systems, and both fluorescence and scattering methods, to quantitatively characterize the pathway leading to membrane permeabilization by pro-apoptotic proteins Bax and Bid. Our measurements show that lipid composition affects specific steps in the pathway. Charged lipids influence the initial recruitment of Bid to the membrane, cardiolipin facilitates protein activation by triggering a conformational change in Bid, and cholesterol blocks Bax insertion into the membrane.

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How cells receive and interpret signals from the outside world is a key question in biology. Most signalling is thought to occur through cell surface receptors that transduce signals across the cell membrane and connect to cytosolic signalling cascades. At variance with this model, cell surface receptors are sometimes observed to translocate into the nucleus of cells. The mechanism for this translocation phenomenon is poorly understood. We found that a bacterial toxin, Pseudomonas Exotoxin also traffics to the nucleus. It accumulates in endosomes that associate with the nuclear envelope of cells, the Nuclear Associated Endosomes (NAE). These endosomes then fuse with the nuclear envelope, eventually leading to material translocation into the nucleoplasm of cells. We found that cell surface receptors such as EGFR and LRP1 traffic to the nucleus by the NAE, which may form the core axis of a novel type of signalling pathways.

Jeremy N. Rich, MD, MHS, MBA. Department of Medicine, Division of Regenerative Medicine, University of California, San Diego, CA 92037 USA

"Dynamic Complexity of Glioma Stem Cells"

Julie Pannequin, Institut de Génomique Fonctionnelle, Montpellier, France.

"Cancer Stem Cells are Key Players in Tumor Recurrence"

Emmanuelle Charafe-Jauffret, Institut Paoli-Calmettes, CRCM, Marseille, France.

"CSC Assays for Personalized Testing of Drug Susceptibility in Advanced Breast Cancer"

Publications : https://www.ncbi.nlm.nih.gov/pubmed/?term=CysterJ

Jason Cyster's lab website: http://cysterlab.ucsf.edu/

Systems approaches are increasingly used to dissect the pathogenesis of diseases and to develop new preventive and therapeutic strategies. One of the major challenges is the curation, integration and analysis of heterogenous data, both from the biomedical research as well as the clinical domain. At the Luxembourg Centre for Systems Biomedicine (LCSB) the research focus is on an interdisciplinary, integrated approach to Parkinson´s disease. In addition to presenting the key elements and examples of our research strategy, some of the key challenges of interdisciplinary research in general will be discussed.  http://wwwen.uni.lu/lcsb/people/rudi_balling

Dr. Dalal’s lab focuses on proteins called histones, which package the entirety of the human genome into a nucleoprotein complex called chromatin in vivo. Specific regions of chromatin are prone to fragility and chromosomal rearrangements in cancer cells. Consequently, understanding how this protein complex is mis-regulated is important in understanding chromosome fragility. Using a combination of chromatin biochemistry, single molecule microscopy, genetics, genomics and cell biology, they are currently investigating whether histone complexes can adopt alternate structural conformations in cancer cells, and the functional consequences of such alterations upon the cancer epigenome.
 
Areas of Expertise
1)       chromatin structure
2)       protein biochemistry
3)       molecular genetics
4)       cell biology
5)       atomic force microscopy
6)       cancer biology
 
For more information :
 https://ccr.cancer.gov/Laboratory-of-Receptor-Biology-and-Gene-Expression/yamini-dalal
 

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Bitplane is the world’s leading interactive microscopy image analysis software company and was founded in 1992 in Switzerland. Through their constant innovation and a clear focus on 3D and 4D image visualization analysis, Bitplane actively shapes the way scientists process multi-dimensional microscopic images.

Imaris includes a set of key tools, which cater for the needs of researchers in live cell imaging, in particular developmental biology, but also in neurobiology where it enables efficient 3D tracing in large images and complicated neural networks. The available tools in Imaris include:

The presentation given by Dr. Georgia Golfis will bring an overview of the latest introduced features in the Imaris software.

Connecting the nucleus to the cytoskeleton is relevant for multiple cellular processes and disruption of these connections result in multiple pathologies. Nuclear positioning within cell cytoplasm requires de connection between nucleus and the cytoskeleton. We are interesting to understand the processes involved in these connections and the role for nuclear positioning in cell function.

We study cell migration and skeletal myofiber formation which required the connection between the nucleus and the cytoskeleton and precise nuclear positioning. We use different molecular and cellular approaches in combination with time-lapse imaging analysis to address these questions.