Biomedical subjects

Florian Fuchs

Publications and source records attributed to Florian Fuchs.

5 recordsLinked to original sources

PubMed2006

Cellular phenotyping by RNAi.

A systematic characterization of genes with unknown function is a key challenge after the sequencing of the human genome and the genomes of many model organisms. High-throughput RNA-interference (RNAi) screenings have become a widely used approach in invertebrate model organisms and also promise to revolutionize cell biology in mammals. Genome-wide RNAi screens in Caenorhabditis elegans and Drosophila, and in a smaller scale in mammalian cells have proven to be a valuable and successful method for the dissection of diverse biological processes. A number of RNAi libraries have become available that rely on different technologies, such as long double-stranded (ds) RNAs, in vitro diced short-interfering (si) RNAs, synthetic siRNAs and short-hairpin (sh) RNAs, which all have specific advantages and disadvantages. In addition, progress in screening technologies and data analysis allows the adaptation of screening methods to analyse more complex cellular processes. This review will summarize strategies in combining genome-scale RNAi libraries, high-throughput screening technologies, integrated high-content data analysis and will discuss future challenges.

Animals↗

PubMed2004

Role of Unc104/KIF1-related motor proteins in mitochondrial transport in Neurospora crassa.

Eukaryotic cells use diverse cytoskeleton-dependent machineries to control inheritance and intracellular positioning of mitochondria. In particular, microtubules play a major role in mitochondrial motility in the filamentous fungus Neurospora crassa and in mammalian cells. We examined the role of two novel Unc104/KIF1-related members of the kinesin family, Nkin2 and Nkin3, in mitochondrial motility in Neurospora. The Nkin2 protein is required for mitochondrial interactions with microtubules in vitro. Mutant hyphae lacking Nkin2 show mitochondrial motility defects in vivo early after germination of conidiospores. Nkin3, a member of a unique fungal-specific subgroup of small Unc104/KIF1-related proteins, is not associated with mitochondria in wild-type cells. However, it is highly expressed and recruited to mitochondria in Deltankin-2 mutants. Mitochondria lacking Nkin2 require Nkin3 for binding to microtubules in vitro, and mitochondrial motility defects in Deltankin-2 mutants disappear with up-regulation of Nkin3 in vivo. We propose that mitochondrial transport is mediated by Nkin2 in Neurospora, and organelle motility defects in Deltankin-2 mutants are rescued by Nkin3. Apparently, a highly versatile complement of organelle motors allows the cell to efficiently respond to exogenous challenges, a process that might also account for the great variety of different mitochondrial transport systems that have evolved in eukaryotic cells.

Animals↗

PubMed2002

Interaction of mitochondria with microtubules in the filamentous fungus Neurospora crassa.

The establishment and maintenance of the 3D structure of eukaryotic cells depends on active transport and positioning of organelles along cytoskeletal elements. The biochemical basis of these processes is only poorly understood. We analysed the interaction of mitochondria with microtubules in the filamentous fungus Neurospora crassa. Mitochondria were fluorescently labelled by expression of matrix-targeted green fluorescent protein. Upon isolation, mitochondria collapsed to round spherical structures that were still able to interact with microtubules in vitro. Binding of mitochondria to microtubules was dependent on peripherally associated proteins on the organellar surface, and was sensitive to adenine nucleotides. MMM1, a mitochondrial outer membrane protein important for maintenance of normal mitochondrial morphology, was not required. This suggests that the interaction of mitochondria with the cytoskeleton is independent of MMM1. We conclude that mitochondrial morphology is maintained by a complex interplay of extrinsic and intrinsic factors, including ATP-dependent proteins on the organellar surface.

Adenosine Triphosphate↗

PubMed2002

Genetic basis of mitochondrial function and morphology in Saccharomyces cerevisiae.

The understanding of the processes underlying organellar function and inheritance requires the identification and characterization of the molecular components involved. We pursued a genomic approach to define the complements of genes required for respiratory growth and inheritance of mitochondria with normal morphology in yeast. With the systematic screening of a deletion mutant library covering the nonessential genes of Saccharomyces cerevisiae the numbers of genes known to be required for respiratory function and establishment of wild-type-like mitochondrial structure have been more than doubled. In addition to the identification of novel components, the systematic screen revealed unprecedented mitochondrial phenotypes that have never been observed by conventional screens. These data provide a comprehensive picture of the cellular processes and molecular components required for mitochondrial function and structure in a simple eukaryotic cell.

Gene Deletion↗

PubMedDate not supplied

Predictive and prognostic factors in small cell lung carcinoma (SCLC)--analysis from routine clinical practice.

BACKGROUND: Prognostic and predictive factors of routine clinical practice among patients with small cell lung carcinoma (SCLC) were evaluated. PATIENTS AND METHODS: Data from 106 patients with SCLC treated by first-line adriamycin, cyclophosphamide and etoposide (ACE) chemotherapy were analyzed. Multivariate analysis was performed. RESULTS: The median overall survival (mOS) of patients was 9.36 months with mOS of 31%, 8% and 3% after 1, 2 and 5 years, respectively. Using multivariate analysis ECOG performance status (p =0.008) and white blood count (WBC) (p=0.022) were independent prognostic factors for mOS. With both, three groups of outcome (good, intermediate, poor) resulting in mOS of 15.8 months, 6.87 months and 3.35 months (p<0.0001) could be established, respectively. The absence of brain metastases (p=0.002), dose reduction (p=0.002) and LDH value (p=0.017) were independent predictive markers. Additionally, female gender was predictive (p=0.025) for complete response (CR). CONCLUSION: Patients with a poor prediction profil might not benefit from ACE chemotherapy. As a consequence, prognostic/predictive factors should be included as stratification criteria in prospective clinical studies.

Antineoplastic Combined Chemotherapy Protocols↗