A5059398577- Genomics and Chromatin Dynamics
- Chromosomal and Genetic Variations
- RNA and protein synthesis mechanisms
- Epigenetics and DNA Methylation
- Cancer-related gene regulation
- Plant Molecular Biology Research
- RNA Research and Splicing
- DNA and Nucleic Acid Chemistry
- Protein Degradation and Inhibitors
- DNA Repair Mechanisms
- Fungal and yeast genetics research
- Ubiquitin and proteasome pathways
- Innovative Energy Harvesting Technologies
- Microtubule and mitosis dynamics
- Histone Deacetylase Inhibitors Research
- RNA Interference and Gene Delivery
- Plant Virus Research Studies
- Radiopharmaceutical Chemistry and Applications
- Enzyme Structure and Function
- Energy Harvesting in Wireless Networks
- Telomeres, Telomerase, and Senescence
- Genomic variations and chromosomal abnormalities
- Hyperglycemia and glycemic control in critically ill and hospitalized patients
- Advanced Sensor and Energy Harvesting Materials
- Redox biology and oxidative stress
University of Leicester
2018-2022
University of Geneva
2014-2021
Institute of Structural and Molecular Biology
2019-2021
ETH Zurich
2003-2017
Cold Spring Harbor Laboratory
2009-2014
Stanford University
2013
Howard Hughes Medical Institute
2009-2013
École Polytechnique Fédérale de Lausanne
2006
Institute for Biomedical Engineering
2005
Max Planck Institute for Medical Research
2004
Chromatin folding determines the accessibility of DNA constituting eukaryotic genomes and consequently is profoundly important in mechanisms nuclear processes such as gene regulation. Nucleosome arrays compact to form a 30-nanometer chromatin fiber hitherto disputed structure. Two competing classes models have been proposed which nucleosomes are either arranged linearly one-start higher order helix or zigzag back forth two-start helix. We analyzed compacted nucleosome stabilized by...
The ATP-dependent integral membrane protease FtsH is universally conserved in bacteria. Orthologs exist chloroplasts and mitochondria, where humans the loss of a close FtsH-homolog causes form spastic paraplegia. plays crucial role quality control by degrading unneeded or damaged proteins, but it also targets soluble signaling factors like sigma(32) lambda-CII. We report here crystal structure construct that functional caseinolytic ATPase assays. molecular architecture this hexameric...
Histone modifications are deposited by chromatin modifying enzymes and read out proteins that recognize the modified state. BRD4-NUT is an oncogenic fusion protein of acetyl lysine reader BRD4 binds to acetylase p300 enables formation long-range intra- interchromosomal interactions. We here examine how acetylation reading writing enable such show NUT contains acidic transcriptional activation domain TAZ2 p300. use NMR investigate structure complex found has autoinhibitory role for NUT-TAZ2...
Chromodomain Helicase DNA binding protein 5 (CHD5) is a tumor suppressor mapping to 1p36, genomic region that frequently deleted in human cancer. Although CHD5 belongs the CHD family of chromatin-remodeling proteins, whether its tumor-suppressive role involves an interaction with chromatin unknown. Here we report Chd5 binds unmodified N terminus H3 through tandem plant homeodomains (PHDs). Genome-wide immunoprecipitation studies reveal preferential loci lacking active mark H3K4me3 and also...
Plants perceive UV-B through the UV RESISTANCE LOCUS 8 (UVR8) photoreceptor and UVR8 activation leads to changes in gene expression such as those associated with acclimation stress tolerance. Albeit functionally unrelated, shows some homology RCC1 (Regulator of Chromatin Condensation 1) proteins from non-plant organisms at sequence level. These act guanine nucleotide exchange factors for Ran GTPases bind chromatin via histones. Subsequent revelation this homology, evidence was presented...
Heterochromatin protein 1 (HP1) proteins are key factors of eukaryotic heterochromatin that coordinate chromatin compaction and transcriptional gene silencing. Through their multivalency they act as adaptors between histone H3 Lys9 di/trimethyl marks in effector complexes bind to the HP1 chromoshadow domain. Most organisms encode for multiple isoforms molecular mechanisms underpin diverse functions genome regulation remain poorly understood. In fission yeast, two Chp2 Swi6 assume distinct...
The SUV39 class of methyltransferase enzymes deposits histone H3 lysine 9 di- and trimethylation (H3K9me2/3), the hallmark constitutive heterochromatin. How these are regulated to mark specific genomic regions as heterochromatic is poorly understood. Clr4 sole H3K9me2/3 in fission yeast Schizosaccharomyces pombe, recent evidence suggests that ubiquitination 14 on (H3K14ub) plays a key role H3K9 methylation. However, molecular mechanism this regulation its heterochromatin formation remain be...
Repressive histone H3 lysine 9 methylation (H3K9me) and its recognition by HP1 proteins are necessary for pericentromeric heterochromatin formation. In Schizosaccharomyces pombe, H3K9me deposition depends on the RNAi pathway. Cryptic loci regulator 4 (Clr4), only known H3K9 methyltransferase in this organism, is a subunit of Clr4 complex (CLRC), whose composition reminiscent CRL4 type cullin-RING ubiquitin ligase (CRL) including cullin Cul4, RING-box protein Pip1, DNA damage binding 1...
While energy harvesting is generally seen to be the key power cyber-physical systems in a low-cost, long-term, efficient manner, it has required large storage devices mitigate effects of source’s variability. The emerging class transiently powered embrace this variability by performing computation proportion harvested, thereby minimizing obtrusive and expensive element. By using an Energy Management Unit (EMU), small bursts can buffered optimally sized capacitor used supply generic loads,...
Methylation of histone H3 at lysine 9 (H3K9) is a hallmark heterochromatin that plays crucial roles in gene silencing, genome stability, and chromosome segregation. In Schizosaccharomyces pombe, Clr4 mediates both di- tri-methylation H3K9. Although H3K9 methylation has been intensely studied mitotic cells, its role during sexual differentiation remains unclear. Here, we map genome-wide meiosis show constitutive temporarily loses H3K9me2 becomes H3K9me3 when cells commit to meiosis. Cells...
Congenital hyperinsulinism/hyperammonemia (HI/HA) syndrome gives rise to unregulated protein-induced insulin secretion from pancreatic beta-cells, fasting hypoglycemia and elevated plasma ammonia levels. Mutations associated with HI/HA were identified in the Glud1 gene, encoding for glutamate dehydrogenase (GDH). We aimed at identifying molecular causes of dysregulation production conferred by most frequent mutation Ser445Leu. Following transduction adenoviruses carrying human GDH-wild type...
State-of-the-art wearable systems are typically performance-constrained, battery-based devices which can, at most, reach self-sustainability using energy harvesting and aggressive duty-cycling. In this work, we present a vision sensor node can reliably execute computationally-intensive computer-vision algorithms in an energy-opportunistic fashion. By leveraging burst-generation scheme, the proposed system efficiently provide guarantees required for tasks with temporal dependencies, even...
Oncogenic histone lysine-to-methionine mutations block the methylation of their corresponding lysine residues on wild-type histones. One attractive model is that these sequester methyltransferases, but genome-wide studies show mutant histones and methyltransferases often do not colocalize. Using chromatin immunoprecipitation sequencing (ChIP-seq), here, we that, in fission yeast, even though H3K9M-containing nucleosomes are broadly distributed across genome, H3K9 methyltransferase Clr4...
The mechanism by which specific protein-DNA complexes induce programmed replication fork stalling in the eukaryotic genome remains poorly understood. In order to shed light on this process we carried out structural investigations essential fission yeast protein Sap1. Sap1 was identified as a involved mating-type switching Schizosaccharomyces pombe, and has been shown be stalling. Interestingly, assumes two different DNA binding modes. At locus dimers of bind SAS1 sequence head-to-head...
Heterochromatin underpins gene repression, genome integrity, and chromosome segregation. In the fission yeast Schizosaccharomyces pombe, conserved protein complexes effect heterochromatin formation via RNA interference-mediated recruitment of a histone H3 lysine 9 methyltransferase to cognate chromatin regions. To identify small molecules that inhibit formation, we performed an in vivo screen for loss silencing dominant selectable kanMX reporter embedded within centromeric heterochromatin....