A5082066799- RNA Research and Splicing
- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- Genetics, Bioinformatics, and Biomedical Research
- Molecular Biology Techniques and Applications
- DNA Repair Mechanisms
- Protein Structure and Dynamics
- Genomics and Chromatin Dynamics
- Nuclear Structure and Function
- Enzyme Structure and Function
- DNA and Nucleic Acid Chemistry
- Neurogenetic and Muscular Disorders Research
- Microtubule and mitosis dynamics
- Protein Degradation and Inhibitors
- Acute Myeloid Leukemia Research
- Amyotrophic Lateral Sclerosis Research
- Ubiquitin and proteasome pathways
- Colorectal and Anal Carcinomas
- Colorectal Cancer Treatments and Studies
- Colorectal Cancer Surgical Treatments
- Cancer-related Molecular Pathways
- Biochemical and Molecular Research
- Lipid metabolism and biosynthesis
- Pickering emulsions and particle stabilization
- Management of metastatic bone disease
Centre Antoine Lacassagne
2024-2025
Institut Gustave Roussy
2024
Inserm
2024
St. Jude Children's Research Hospital
2014-2023
Institutul Oncologic Bucuresti
2022-2023
Children's Research Hospital
2020
SUNY Upstate Medical University
2006-2010
Massachusetts Institute of Technology
2009
The nucleolus is a membrane-less organelle formed through liquid-liquid phase separation of its components from the surrounding nucleoplasm. Here, we show that nucleophosmin (NPM1) integrates within via multi-modal mechanism involving multivalent interactions with proteins containing arginine-rich linear motifs (R-motifs) and ribosomal RNA (rRNA). Importantly, these R-motifs are found in canonical nucleolar localization signals. Based on novel combination biophysical approaches, propose...
Nucleophosmin (NPM1) is an abundant, oligomeric protein in the granular component of nucleolus with roles ribosome biogenesis. Pentameric NPM1 undergoes liquid-liquid phase separation (LLPS) via heterotypic interactions nucleolar components, including ribosomal RNA (rRNA) and proteins which display multivalent arginine-rich linear motifs (R-motifs), integral to liquid-like matrix. Here we show that can also undergo LLPS homotypic between its polyampholytic intrinsically disordered regions, a...
NUP98 fusion oncoproteins (FO) are drivers in pediatric leukemias and many transform hematopoietic cells. Most FOs harbor an intrinsically disordered region from that is prone to liquid-liquid phase separation (LLPS) vitro. A predominant class of FOs, including NUP98-HOXA9 (NHA9), retains a DNA-binding homeodomain, whereas others other types DNA- or chromatin-binding domains. have long been known form puncta, but long-standing questions how nuclear puncta they drive leukemogenesis. Here we...
In the past almost 15 years, we witnessed birth of a new scientific field focused on existence, formation, biological functions, and disease associations membraneless bodies in cells, now referred to as biomolecular condensates. Pioneering studies from several laboratories [reviewed in1, 2, 3] supported model wherein condensates associated with diverse processes form through process phase separation. These other findings that followed have revolutionized our understanding how biomolecules...
Abstract The functions of biomolecular condensates are thought to be influenced by their material properties, and these will determined the internal organization molecules within condensates. However, structural characterizations challenging, rarely reported. Here, we deploy a combination small angle neutron scattering, fluorescence recovery after photobleaching, coarse-grained molecular dynamics simulations provide descriptions model that formed macromolecules from nucleolar granular...
Significance Nucleophosmin (NPM1) is a multifunctional protein with critical roles in ribosome biogenesis, centrosome duplication, and tumor suppression. Despite the established importance of NPM1 as marker potential drug target, little currently known about molecular mechanisms that govern its various functions. Our manuscript describes N-terminal domain (Npm-N) exhibits phosphorylation-dependent structural polymorphism along broad conformational landscape between two extreme states:...
The nucleolus, the site for ribosome biogenesis contains hundreds of proteins and several types RNA. functions many non-ribosomal nucleolar are poorly understood, including Surfeit locus protein 6 (SURF6), an essential disordered with roles in cell proliferation. SURF6 co-localizes Nucleophosmin (NPM1), a highly abundant that mediates liquid-like features granular component region nucleolus through phase separation. Here, we show electrostatically-driven interactions between regions NPM1...
Abstract Fusion oncoproteins (FOs) arise from chromosomal translocations in ~17% of cancers and are often oncogenic drivers. Although some FOs can promote oncogenesis by undergoing liquid-liquid phase separation (LLPS) to form aberrant biomolecular condensates, the generality this phenomenon is unknown. We explored question testing 166 HeLa cells found that 58% formed condensates. The condensate-forming displayed physicochemical features distinct those condensate-negative segregated into...
Abstract The discovery of biomolecular condensates transformed our understanding intracellular compartmentalization molecules. To integrate interdisciplinary scientific knowledge about the function and composition condensates, we developed crowdsourcing condensate database encyclopedia ( cd-code.org ). CD-CODE is a community-editable platform, which includes based on literature, an relevant terms web application. Our platform will accelerate validation facilitate efforts to understand their...
Pneumococcus, meningococcus, and Haemophilus influenzae cause a similar spectrum of infections in the ear, lung, blood, brain. They share cross-reactive antigens that bind to laminin receptor blood-brain barrier as molecular basis for neurotropism, this step pathogenesis was addressed vaccine design. Biologically active peptides derived from choline-binding protein A (CbpA) pneumococcus were identified then genetically fused L460D pneumolysoid. The fusion construct tested efficacy mouse...
Existing strategies for creating biosensors mainly rely on large conformational changes to transduce a binding event an output signal. Most molecules, however, do not exhibit large-scale structural upon substrate binding. Here, we present general approach (alternate frame folding, or AFF) engineering allosteric control into ligand proteins. AFF can in principle be applied any protein establish binding-induced change, even if none exists the natural molecule. The design duplicates portion of...