Noa Katz is a Stanford Science Fellow and an EMBO scholar at Stanford University. She designs and implements biomolecular gene circuits to study and manipulate the central nervous system to promote therapeutic applications for neuro-regeneration and autism.
Honors & Awards
Stanford Science Fellow, Stanford University (2022-present)
Postdoctoral Fellowship, European Molecular Biology Organization (2022-present)
Postdoctoral Award, Israel National Postdoctoral Award for Advancing Women in Science (2021-present)
Postdoctoral Fellowship, Fulbright (2021-2022)
Conference Scholarship, Keystone Symposia- Noncoding RNAs in Health and Disease (2016)
Best Presentation, 2nd Synthetic Systems Biology Summer School (2015)
Special Doctorate Program for outstanding BSc graduates, Technion, Israel Institute of Technology (2013-2019)
Bachelor of Science, highest honors, Technion, Israel Institute of Technology (2013)
Excellence Scholarship, PEF Israel Endowment Funds (2009-2012)
Roee Amit, Noa Katz. "United States Patent 20210095296 Synthetic non-coding RNAs", TECHNION RESEARCH & DEVELOPMENT FOUNDATION LTD., Apr 1, 2021
Roee Amit, Alexey Tomsov, Orna Atar, Liron Abrahami, Yael Annis, Roni Cohen, Alexandra Ereskovsky, Noa Katz, Lior Levy, Maayan Lufton, Tal Ofek, Sagi Sheinkman, Nitzan Shmuel, Inbal Vaknin, Ruth Veksler, Adi Yannai. "United States Patent 10240132 Composition and method for treating androgen-dependent disorders", TECHNION RESEARCH & DEVELOPMENT FOUNDATION LTD., Mar 26, 2019
Modular, programmable RNA sensing using ADAR editing in living cells.
With the increasing availability of single-cell transcriptomes, RNA signatures offer a promising basis for targeting living cells. Molecular RNA sensors would enable the study of and therapeutic interventions for specific cell types/states in diverse contexts, particularly in human patients and non-model organisms. Here we describe a modular, programmable system for live RNA sensing using adenosine deaminases acting on RNA (RADAR). We validate, and then expand, our basic design, characterize its performance, and analyze its compatibility with human and mouse transcriptomes. We identify strategies to boost output levels and improve the dynamic range. Additionally, we show that RADAR enables compact AND logic. In addition to responding to transcript levels, RADAR can distinguish disease-relevant sequence alterations of transcript identities, such as point mutations and fusions. Finally, we demonstrate that RADAR is a self-contained system with the potential to function in diverse organisms.
View details for DOI 10.1038/s41587-022-01493-x
View details for PubMedID 36198772
A Cell-Free Assay for Rapid Screening of Inhibitors of hACE2-Receptor-SARS-CoV-2-Spike Binding
ACS SYNTHETIC BIOLOGY
2022; 11 (4): 1389-1396
We present a cell-free assay for rapid screening of candidate inhibitors of protein binding, focusing on inhibition of the interaction between the SARS-CoV-2 Spike receptor binding domain (RBD) and human angiotensin-converting enzyme 2 (hACE2). The assay has two components: fluorescent polystyrene particles covalently coated with RBD, termed virion-particles (v-particles), and fluorescently labeled hACE2 (hACE2F) that binds the v-particles. When incubated with an inhibitor, v-particle-hACE2F binding is diminished, resulting in a reduction in the fluorescent signal of bound hACE2F relative to the noninhibitor control, which can be measured via flow cytometry or fluorescence microscopy. We determine the amount of RBD needed for v-particle preparation, v-particle incubation time with hACE2F, hACE2F detection limit, and specificity of v-particle binding to hACE2F. We measure the dose response of the v-particles to known inhibitors. Finally, utilizing an RNA-binding protein tdPP7 incorporated into hACE2F, we demonstrate that RNA-hACE2F granules trap v-particles effectively, providing a basis for potential RNA-hACE2F therapeutics.
View details for DOI 10.1021/acssynbio.1c00381
View details for Web of Science ID 000791641700002
View details for PubMedID 35377616
View details for PubMedCentralID PMC9003891
Overcoming the design, build, test bottleneck for synthesis of nonrepetitive protein-RNA cassettes
2021; 12 (1): 1576
We apply an oligo-library and machine learning-approach to characterize the sequence and structural determinants of binding of the phage coat proteins (CPs) of bacteriophages MS2 (MCP), PP7 (PCP), and Qβ (QCP) to RNA. Using the oligo library, we generate thousands of candidate binding sites for each CP, and screen for binding using a high-throughput dose-response Sort-seq assay (iSort-seq). We then apply a neural network to expand this space of binding sites, which allowed us to identify the critical structural and sequence features for binding of each CP. To verify our model and experimental findings, we design several non-repetitive binding site cassettes and validate their functionality in mammalian cells. We find that the binding of each CP to RNA is characterized by a unique space of sequence and structural determinants, thus providing a more complete description of CP-RNA interaction as compared with previous low-throughput findings. Finally, based on the binding spaces we demonstrate a computational tool for the successful design and rapid synthesis of functional non-repetitive binding-site cassettes.
View details for DOI 10.1038/s41467-021-21578-6
View details for Web of Science ID 000629597700001
View details for PubMedID 33707432
View details for PubMedCentralID PMC7952577
Synthetic 5 ' UTRs Can Either Up- or Downregulate Expression upon RNA-Binding Protein Binding
2019; 9 (1): 93-+
The construction of complex gene-regulatory networks requires both inhibitory and upregulatory modules. However, the vast majority of RNA-based regulatory "parts" are inhibitory. Using a synthetic biology approach combined with SHAPE-seq, we explored the regulatory effect of RNA-binding protein (RBP)-RNA interactions in bacterial 5' UTRs. By positioning a library of RNA hairpins upstream of a reporter gene and co-expressing them with the matching RBP, we observed a set of regulatory responses, including translational stimulation, translational repression, and cooperative behavior. Our combined approach revealed three distinct states in vivo: in the absence of RBPs, the RNA molecules can be found in either a molten state that is amenable to translation or a structured phase that inhibits translation. In the presence of RBPs, the RNA molecules are in a semi-structured phase with partial translational capacity. Our work provides new insight into RBP-based regulation and a blueprint for designing complete gene-regulatory circuits at the post-transcriptional level.
View details for DOI 10.1016/j.cels.2019.04.007
View details for Web of Science ID 000483321900009
View details for PubMedID 31129060
An Assay for Quantifying Protein-RNA Binding in Bacteria
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
In the initiation step of protein translation, the ribosome binds to the initiation region of the mRNA. Translation initiation can be blocked by binding of an RNA binding protein (RBP) to the initiation region of the mRNA, which interferes with ribosome binding. In the presented method, we utilize this blocking phenomenon to quantify the binding affinity of RBPs to their cognate and non-cognate binding sites. To do this, we insert a test binding site in the initiation region of a reporter mRNA and induce the expression of the test RBP. In the case of RBP-RNA binding, we observed a sigmoidal repression of the reporter expression as a function of RBP concentration. In the case of no-affinity or very low affinity between binding site and RBP, no significant repression was observed. The method is carried out in live bacterial cells, and does not require expensive or sophisticated machinery. It is useful for quantifying and comparing between the binding affinities of different RBPs that are functional in bacteria to a set of designed binding sites. This method may be inappropriate for binding sites with high structural complexity. This is due to the possibility of repression of ribosomal initiation by complex mRNA structure in the absence of RBP, which would result in lower basal reporter gene expression, and thus less-observable reporter repression upon RBP binding.
View details for DOI 10.3791/59611
View details for Web of Science ID 000473295900072
View details for PubMedID 31259904
Designing Bacterial Chemotactic Receptors Guided by Photonic Femtoliter Well Arrays for Quantifiable, Label-Free Measurement of Bacterial Chemotaxis
ACS BIOMATERIALS SCIENCE & ENGINEERING
2019; 5 (2): 603-612
Whole cell bioreporters, such as bacterial cells, can be used for environmental and clinical sensing of specific analytes. However, the current methods implemented to observe such bioreporters in the form of chemotactic responses heavily rely on microscope analysis, fluorescent labels, and hard-to-scale microfluidic devices. Herein, we demonstrate that chemotaxis can be detected within minutes using intrinsic optical measurements of silicon femtoliter well arrays (FMAs). This is done via phase-shift reflectometric interference spectroscopic measurements (PRISM) of the wells, which act as silicon diffraction gratings, enabling label-free, real-time quantification of the number of trapped bacteria cells in the optical readout. By generating unsteady chemical gradients over the wells, we first demonstrate that chemotaxis toward attractants and away from repellents can be easily differentiated based on the signal response of PRISM. The lowest concentration of chemorepellent to elicit an observed bacterial response was 50 mM, whereas the lowest concentration of chemoattractant to elicit a response was 10 mM. Second, we employed PRISM, in combination with a computational approach, to rapidly scan for and identify a novel synthetic histamine chemoreceptor strain. Consequently, we show that by using a combined computational design approach, together with a quantitative, real-time, and label-free detection method, it is possible to manufacture and characterize novel synthetic chemoreceptors in Escherichia coli (E. coli).
View details for DOI 10.1021/acsbiomaterials.8b01429
View details for Web of Science ID 000458937900022
View details for PubMedID 33405824
An in Vivo Binding Assay for RNA-Binding Proteins Based on Repression of a Reporter Gene
ACS SYNTHETIC BIOLOGY
2018; 7 (12): 2765-2774
We study translation repression in bacteria by engineering a regulatory circuit that functions as a binding assay for RNA binding proteins (RBP) in vivo. We do so by inducing expression of a fluorescent protein-RBP chimera, together with encoding its binding site at various positions within the ribosomal initiation region (+11-13 nt from the AUG) of a reporter module. We show that when bound by their cognate RBPs, the phage coat proteins for PP7 (PCP) and Qβ (QCP), strong repression is observed for all hairpin positions within the initiation region. Yet, a sharp transition to no-effect is observed when positioned in the elongation region, at a single-nucleotide resolution. Employing in vivo Selective 2'-hydroxyl acylation analyzed by primer extension followed by sequencing (SHAPE-seq) for a representative construct, established that in the translationally active state the mRNA molecule is nonstructured, while in the repressed state a structured signature was detected. We then utilize this regulatory phenomena to quantify the binding affinity of the coat proteins of phages MS2, PP7, GA, and Qβ to 14 cognate and noncognate binding sites in vivo. Using our circuit, we demonstrate qualitative differences between in vitro to in vivo binding characteristics for various variants when comparing to past studies. Furthermore, by introducing a simple mutation to the loop region for the Qβ-wt site, MCP binding is abolished, creating the first high-affinity QCP site that is completely orthogonal to MCP. Consequently, we demonstrate that our hybrid transcriptional-post-transcriptional circuit can be utilized as a binding assay to quantify RNA-RBP interactions in vivo.
View details for DOI 10.1021/acssynbio.8b00378
View details for Web of Science ID 000454568100008
View details for PubMedID 30408420