Nadine Czudnochowski
A5051784673- RNA and protein synthesis mechanisms
- SARS-CoV-2 and COVID-19 Research
- Animal Virus Infections Studies
- RNA Research and Splicing
- HIV Research and Treatment
- RNA modifications and cancer
- Viral gastroenteritis research and epidemiology
- Reproductive tract infections research
- Biochemical and Molecular Research
- Virus-based gene therapy research
- RNA Interference and Gene Delivery
- Monoclonal and Polyclonal Antibodies Research
- Clostridium difficile and Clostridium perfringens research
- Mycobacterium research and diagnosis
- Urinary Tract Infections Management
- ATP Synthase and ATPases Research
- Tuberculosis Research and Epidemiology
- Bacterial Genetics and Biotechnology
- Bacteriophages and microbial interactions
- Lipid Membrane Structure and Behavior
- Viral Infections and Immunology Research
- Metalloenzymes and iron-sulfur proteins
- Zeolite Catalysis and Synthesis
- Complement system in diseases
- COVID-19 Clinical Research Studies
VIR Biotechnology (United States)
2021-2023
University of California, San Francisco
2013-2022
Chan Zuckerberg Initiative (United States)
2019
Microbial ID (United States)
2019
Technion – Israel Institute of Technology
2013
Max Planck Institute of Molecular Physiology
2007-2012
Max Planck Society
2007-2012
University of Sheffield
2006
An ideal therapeutic anti-SARS-CoV-2 antibody would resist viral escape
Abstract Currently circulating SARS-CoV-2 variants have acquired convergent mutations at hot spots in the receptor-binding domain 1 (RBD) of spike protein. The effects these on viral infection and transmission efficacy vaccines therapies remains poorly understood. Here we demonstrate that recently emerged BQ.1.1 XBB.1.5 bind host ACE2 with high affinity promote membrane fusion more efficiently than earlier Omicron variants. Structures BQ.1.1, XBB.1 BN.1 RBDs bound to fragment antigen-binding...
Phosphorylation of RNA polymerase II carboxy-terminal domain (CTD) in hepta-repeats YSPTSPS regulates eukaryotic transcription. Whereas Ser5 is phosphorylated the initiation phase, Ser2 phosphorylation marks elongation state. Here we show that positive transcription factor P-TEFb a CTD kinase unable to create Ser2/Ser5 double phosphorylations, while it exhibits fourfold higher activity on substrate pre-phosphorylated at Ser7 compared with consensus hepta-repeat or YSPTSPK variant. Mass...
Human immunodeficiency virus type 1 (HIV-1) transcriptional transactivator (Tat) recruits the positive transcription elongation factor b (P-TEFb) to viral promoter. Consisting of cyclin dependent kinase 9 (Cdk9) and T1, P-TEFb phosphorylates RNA polymerase II negative stimulate HIV-1 genes. A major fraction nuclear is sequestered into a transcriptionally inactive 7SK small ribonucleoprotein (snRNP) by coordinated actions (snRNA) hexamethylene bisacetamide (HMBA) induced protein (HEXIM1). In...
Currently circulating SARS-CoV-2 variants acquired convergent mutations at receptor-binding domain (RBD) hot spots 1 . Their impact on viral infection, transmission, and efficacy of vaccines therapeutics remains poorly understood. Here, we demonstrate that recently emerged BQ.1.1. XBB.1 bind ACE2 with high affinity promote membrane fusion more efficiently than earlier Omicron variants. Structures the BQ.1.1 RBDs bound to human S309 Fab (sotrovimab parent) explain altered recognition...
Chlamydia trachomatis is an obligate intracellular pathogen that resides in a membrane-bound compartment, the inclusion. The bacteria secrete unique class of proteins, Incs, which insert into inclusion membrane and modulate host-bacterium interface. We previously reported IncE binds specifically to Sorting Nexin 5 Phox domain (SNX5-PX) disrupts retromer trafficking. Here, we present crystal structure SNX5-PX:IncE complex, showing bound highly conserved hydrophobic groove on SNX5. Mutagenesis...
The recently emerged SARS-CoV-2 Omicron variant harbors 37 amino acid substitutions in the spike (S) protein, 15 of which are receptor-binding domain (RBD), thereby raising concerns about effectiveness available vaccines and antibody therapeutics. Here, we show that RBD binds to human ACE2 with enhanced affinity relative Wuhan-Hu-1 acquires binding mouse ACE2. Severe reductions plasma neutralizing activity were observed against compared ancestral pseudovirus for vaccinated convalescent...
The cell envelope of Mycobacterium tuberculosis , the bacterium that causes disease tuberculosis, is a complex structure composed abundant lipids and glycolipids, including signature lipid these bacteria, mycolic acids. In this study, we identified two new components transport machinery constructs wall. These accessory proteins are in with MmpL3 transporter. One proteins, TtfA, required for acid viability, whereas other stabilizes complex. studies identify essential biosynthetic mycobacteria.
The recent emergence of SARS-CoV-2 variants concern (VOC) and the recurrent spillovers coronaviruses in human population highlight need for broadly neutralizing antibodies that are not affected by ongoing antigenic drift can prevent or treat future zoonotic infections. Here, we describe a monoclonal antibody (mAb), designated S2X259, recognizing highly conserved cryptic receptor-binding domain (RBD) epitope cross-reacting with spikes from all sarbecovirus clades. S2X259 neutralizes...
Hemolysin E (HlyE, ClyA, SheA) is a pore-forming protein toxin isolated from Escherichia coli. The three-dimensional structure of its water-soluble form known, but that the membrane-bound HlyE complex not. We have used electron microscopy and image processing to show pores are predominantly octameric. Three-dimensional reconstructions assembled in lipid/detergent micelles suggest degree conformational variability octameric complexes. reconstructed were significantly longer than maximum...
Abstract An ideal anti-SARS-CoV-2 antibody would resist viral escape 1–3 , have activity against diverse SARS-related coronaviruses 4–7 and be highly protective through neutralization 8–11 effector functions 12,13 . Understanding how these properties relate to each other vary across epitopes aid development of therapeutics guide vaccine design. Here, we comprehensively characterize escape, breadth, potency a panel SARS-CoV-2 antibodies targeting the receptor-binding domain (RBD), including...
RluB catalyses the modification of U2605 to pseudouridine (Ψ) in a stem-loop at peptidyl transferase center Escherichia coli 23S rRNA. The homolog RluF is specific adjacent nucleotide stem, U2604. 1.3 Å resolution crystal structure complex between catalytic domain and isolated substrate stem-loop, which target uridine substituted by 5-fluorouridine (5-FU), reveals covalent bond isomerized base tyrosine 140. compared with alone determined 2.5 resolution. RluB-bound has essentially same...
An ideal anti-SARS-CoV-2 antibody would resist viral escape 1-3 , have activity against diverse SARS-related coronaviruses 4-7 and be highly protective through neutralization 8-11 effector functions 12,13 . Understanding how these properties relate to each other vary across epitopes aid development of therapeutics guide vaccine design. Here, we comprehensively characterize escape, breadth, potency a panel SARS-CoV-2 antibodies targeting the receptor-binding domain (RBD), including S309 4...
The repeated spillovers of β-coronaviruses in humans along with the rapid emergence SARS-CoV-2 escape variants highlight need to develop broad coronavirus therapeutics and vaccines. Five monoclonal antibodies (mAbs) were isolated from COVID-19 convalescent individuals found cross-react multiple β-coronavirus spike (S) glycoproteins by targeting stem helix. One these mAbs, S2P6, cross-reacts more than twenty human animal S broadly neutralizes pseudotyped viruses sarbecovirus, merbecovirus...
Abstract Mycolic acids are the signature lipid of mycobacteria and constitute an important physical component cell wall, a target mycobacterial specific antibiotics, mediator M. tuberculosis pathogenesis. synthesized in cytoplasm thought to be transported wall as trehalose ester by MmpL3 transporter, antibiotic for . However, mechanism which mycolate synthesis is coupled transport, full transport machinery, unknown. Here we identify two new components machinery mycobacteria. The protein...
Abstract The ESX (or Type VII) secretion systems are protein export in mycobacteria and many Gram-positive bacteria that mediate a broad range of functions including virulence, conjugation, metabolic regulation. These translocate folded dimers WXG100-superfamily substrates across the cytoplasmic membrane; however, architecture mechanism translocation has remained elusive. We report cryo-electron microscopy structure an ESX-3 system, purified using epitope tag inserted with recombineering...
Science education and research have the potential to drive profound change in low- middle-income countries (LMICs) through encouraging innovation, attracting industry, creating job opportunities. However, LMICs, capacity is often limited, acquisition of funding access state-of-the-art technologies challenging. The Alliance for Global Health (the Alliance) was founded as a partnership between University California, Berkeley (USA) Makerere (Uganda), with goal strengthening University's...