A5025564172- CRISPR and Genetic Engineering
- RNA and protein synthesis mechanisms
- Cellular transport and secretion
- Pluripotent Stem Cells Research
- Mosquito-borne diseases and control
- Advanced biosensing and bioanalysis techniques
- Protein Degradation and Inhibitors
- Viral Infections and Immunology Research
- Peptidase Inhibition and Analysis
- Chromosomal and Genetic Variations
- Drug Transport and Resistance Mechanisms
- Cytomegalovirus and herpesvirus research
- Ion Transport and Channel Regulation
- interferon and immune responses
- Ubiquitin and proteasome pathways
- RNA regulation and disease
- Erythrocyte Function and Pathophysiology
- Evolution and Genetic Dynamics
- Insect symbiosis and bacterial influences
- Phagocytosis and Immune Regulation
- Cancer-related gene regulation
- Immune Response and Inflammation
- RNA Research and Splicing
- Adenosine and Purinergic Signaling
- Innovation and Socioeconomic Development
CeMM Research Center for Molecular Medicine
2018-2025
Austrian Academy of Sciences
2018-2025
Massachusetts Institute of Technology
2015-2017
McGovern Institute for Brain Research
2015-2017
Broad Institute
2015-2017
Sensitive and specific CRISPR diagnostics Methods are needed that can easily detect nucleic acids signal the presence of pathogens, even at very low levels. Gootenberg et al. combined allele-specific sensing ability CRISPR-Cas13a with recombinase polymerase amplification methods to RNA DNA sequences. The method successfully detected attomolar levels Zika virus, as well pathogenic bacteria. It could also be used perform human genotyping from cell-free DNA. Science , this issue p. 438
Near-haploid human cell lines are instrumental for genetic screens and genome engineering as gene inactivation is greatly facilitated by the absence of a second copy. However, no completely haploid line has been described, hampering accessibility subset genes. The near-haploid HAP1 contains single copy all chromosomes except heterozygous 30-megabase fragment Chromosome 15. This large encompasses 330 genes integrated on long arm 19. Here, we employ CRISPR/Cas9-based strategy to excise this...
With more than 450 members, the solute carrier (SLC) group of proteins represents largest class transporters encoded in human genome. Their several-pass transmembrane domain structure and hydrophobicity contribute to orphan status many SLCs, devoid known cargos or chemical inhibitors. We report that SLC belonging different families subcellular compartments are amenable induced degradation by heterobifunctional ligands. Engineering endogenous alleles via tag (dTAG) technology enabled control...
Macrophages represent the first line of immune defense against pathogens, and phagosome acidification is a necessary step in pathogen clearance. Here, we identified bicarbonate transporter SLC4A7, which strongly induced upon macrophage differentiation, as critical for acidification. Loss SLC4A7 reduced phagocytosed beads or bacteria impaired intracellular microbicidal capacity human cell lines. The phenotype was rescued by wild-type but not mutants, affecting transport surface localization....
Proteolysis targeting chimeras (PROTACs) are bifunctional molecules that induce selective protein degradation by linking an E3 ubiquitin ligase enzyme to a target protein. This approach allows scope for "undruggable" proteins, and several PROTACs have reached the stage of clinical candidates. However, roles cellular transmembrane transporters in PROTAC uptake efflux remain underexplored. Here, we utilized transporter-focused genetic screens identify ATP-binding cassette transporter...
Abstract The mutagenic repair of Cas9 generated breaks is thought to predominantly rely on non-homologous end-joining (NHEJ), leading insertions and deletions within DNA that culminate in gene knock-out (KO). In this study, by taking focused as well genome-wide approaches, we show pathway dispensable for the such lesions. Genetic ablation NHEJ fully compensated alternative end joining (alt-EJ), a POLQ-dependent manner, resulting distinct signature with larger may be exploited large-scale...
CRISPR-Cas adaptive immune systems defend microbes against foreign nucleic acids via RNA-guided endonucleases. Using a computational sequence database mining approach, we identify two Class 2 (subtype VI-B) that lack Cas1 and Cas2 encompass single large effector protein, Cas13b, along with one of previously uncharacterized associated proteins, Csx27 or Csx28. We establish these can achieve RNA interference when heterologously expressed. Through combination biochemical genetic experiments,...
Phagocytosis, the process by which cells engulf large particles, plays a vital role in driving tissue clearance and host defense. Its dysregulation is connected to autoimmunity, toxic accumulation of proteins, increased risks for infections. Despite its importance, we lack full understanding all molecular components involved process. To create functional map human cells, performed genome-wide CRISPRko FACS screen that identified 716 genes. Mapping those hits comprehensive protein–protein...
Abstract Phagocytosis, the process of engulfing large particles by cells, is a multilayered biological activity driving tissue clearance and host defense. Dysregulation phagocytosis connected to autoimmunity, accumulation toxic disease proteins, increased risks for infections. Despite its importance multiple roles, we lack full understanding cellular machinery involved in executing regulating process, including coordination with other events. To create functional map human performed...