A5012853684- Monoclonal and Polyclonal Antibodies Research
- Axon Guidance and Neuronal Signaling
- Viral Infectious Diseases and Gene Expression in Insects
- Protein purification and stability
- Glycosylation and Glycoproteins Research
- Neurogenesis and neuroplasticity mechanisms
- Cancer-related gene regulation
- Neuroscience and Neuropharmacology Research
- T-cell and B-cell Immunology
- Zebrafish Biomedical Research Applications
- Cancer Genomics and Diagnostics
- Virus-based gene therapy research
- CAR-T cell therapy research
- Retinal Development and Disorders
- RNA modifications and cancer
- Genomic variations and chromosomal abnormalities
- Cancer Cells and Metastasis
- Bioactive Compounds and Antitumor Agents
- Celiac Disease Research and Management
- Cardiac Ischemia and Reperfusion
- Heat shock proteins research
- Hepatitis B Virus Studies
- Cancer-related molecular mechanisms research
- NF-κB Signaling Pathways
- CRISPR and Genetic Engineering
Roche Pharma AG (Germany)
2010-2025
La Roche College
2017
Roche (Switzerland)
2010-2015
Max Planck Society
1993-1997
Max Planck Institute for Developmental Biology
1993-1996
Max Planck Institute of Biochemistry
1995
TH Bingen University of Applied Sciences
1994
We have isolated mutants in the zebrafish Danio rerio that defects axonal connectivity between retina and tectum. 5-day-old fish larvae were screened by labeling retinal ganglion cells with DiI DiO observing their projections to on 82 mutations, representing 13 complementation groups 6 single allele loci, found cell axon pathfinding These genes fall into five classes, based location of errors eye In Class I mutant (belladonna, detour, you-too, iguana, umleitung, blowout) axons grow directly...
A systematic search for mutations affecting the retinotectal projection in zebrafish larvae was performed, as part of large-scale Tubingen screen homozygous diploid mutants embryonic development. 2,746 inbred lines (F2 families) from males mutagenized with ethylnitroso urea were screened. In wild-type larvae, developing retinal axons travel along a stereotyped route to contralateral optic tectum. Here, their terminals form highly ordered retinotopic map. To detect deviations this pattern, an...
Monoclonal antibodies (mAbs) and proteins containing antibody domains are the most prevalent class of biotherapeutics in diverse indication areas. Today, established techniques such as immunization or phage display allow for an efficient generation new mAbs. Besides functional properties, stability future therapeutic mAbs is a key selection criterion which essential development drug candidate into marketed product. Therapeutic may degrade via asparagine (Asn) deamidation aspartate (Asp)...
Retinal ganglion cells connect to their target organ, the rectum, in a highly ordered fashion. We performed large-scale screen for mutations affecting retinotectal projection of zebrafish, which resulted identification 114 mutations. 44 these disturb either order RGC axons optic nerve and tract, establishment topographic map on tectum, or formation proper termination fields. Mutations three genes, boxer, dackel pinscher, disrupt sorting tract but do not affect mapping tectum. In mutants,...
We have developed a robust platform to generate and functionally characterize rabbit-derived antibodies using B cells from peripheral blood. The rapid high throughput procedure generates diverse set of antibodies, yet requires only few animals be immunized without the need sacrifice them. workflow includes (i) identification isolation single rabbit blood expressing IgG (ii) an elaborate short term B-cell cultivation produce sufficient monoclonal antigen specific for comprehensive phenotype...
Loops are often vital for protein function, however, their irregular structures make them difficult to model accurately. Current loop modelling algorithms can mostly be divided into two categories: knowledge-based, where databases of fragments searched find suitable conformations and ab initio, generated computationally. Existing knowledge-based methods only use that the same length as target, even though loops slightly different lengths may adopt similar conformations. Here, we present a...
Complementarity-determining regions (CDRs) are antibody loops that make up the antigen binding site. Here, we show all CDR types have structurally similar of different lengths. Based on these findings, created length-independent canonical classes for non-H3 CDRs. Our length variable structural clusters strong sequence patterns suggesting either they evolved from same original structure or result some form convergence. We find our method not only a larger number CDRs, but also predicts class...
In the dynamic field of gene therapy, recombinant adeno-associated viruses (rAAVs) have become leading viral vectors due to their safety, long-term expression, and wide-ranging cell tissue tropism. With numerous FDA approvals commercial products underscoring potential, there is a critical need for efficient production processes achieve high vector titers quality. A major challenge in rAAV packaging genome into capsid, with empty or partially filled capsids often representing over 90%...
Biotherapeutics may contain a multitude of different post-translational modifications (PTMs) that need to be assessed and possibly monitored controlled ensure reproducible product quality. During early development biotherapeutics, unexpected PTMs might prevented by in silico identification characterization together with further molecular engineering. Mass determinations human IgG1 (mAb1) bispecific IgG-ligand fusion protein (BsAbA) demonstrated the presence unusual resulting major +80 Da,...
Antibodies are generated with great diversity in nature resulting a set of molecules, each optimized to bind specific target. Taking advantage their and specificity, antibodies make up for large part recently developed biologic drugs. For therapeutic use need fulfill several criteria be safe efficient. Polyspecific can structurally unrelated molecules addition main target, which lead side effects decreased efficacy setting, example via reduction effective drug levels. Therefore, we created...
Knowledge of the 3-dimensional structure antigen-binding region antibodies enables numerous useful applications regarding design and development antibody-based drugs. We present a knowledge-based antibody prediction methodology that incorporates concepts have arisen from an applied engineering environment. The protocol exploits rich continuously growing supply experimentally derived structures available to predict CDR loop conformations packing heavy light chain quickly without user...
Abstract Substrate‐bound guidance cues play an important role during the development of thalamocortical projections. We used time‐lapse video microscopy to study growth behaviour thalamic axons on different substrates. On embryonic cortical membranes and a pure laminin substrate, fibres advanced relatively slowly (∼15 μm/h) average their cones retracted transiently every ∼5 h. In contrast, prepared from early postnatal cortex, grew twice as fast spontaneous cone collapse occurred ∼8 times...
Numerous studies have shown that the developing tip of a neurite, growth cone, can respond to environmental cues with behaviors such as guidance or collapse. To assess whether given cell type use more than one second-messenger pathway for single behavior, we compared influence two well-characterized on cones chick temporal retinal ganglion cells. The first cue was repulsive activity derived from posterior optic tectum (p-membranes), and second collapse-inducing oligodendrocytes known...
Sequence variations are being studied for a better understanding of the mechanism and development cancer as mutation-driven disease. The systematic sequencing genes in tumors technological advances high-throughput techniques combined with efficient data acquisition methods have resulted an explosion available genome-related data. Despite progress increase data, improvements application area, example, drug target discovery, failed to keep pace increased research spending. One reason this...
Cancer is a disease of genome alterations that arise through the acquisition multiple somatic DNA sequence mutations. Some these mutations can be critical for development tumor and useful to characterize types or predict outcome.We have constructed an integrated biological information system termed Roche Genome Database (RCGDB) combining different human mutation databases already publicly available. This data further extended by hand-curated from publications.The current version RCGDB...