A5017505256- Eosinophilic Esophagitis
- IL-33, ST2, and ILC Pathways
- Corneal surgery and disorders
- RNA and protein synthesis mechanisms
- Corneal Surgery and Treatments
- AI in cancer detection
- Microbial Metabolic Engineering and Bioproduction
- Fungal and yeast genetics research
- Protein Structure and Dynamics
- Reproductive System and Pregnancy
- Computational Drug Discovery Methods
- Ocular Surface and Contact Lens
- Bacterial Genetics and Biotechnology
- Eosinophilic Disorders and Syndromes
- Cell Image Analysis Techniques
- Genomics and Chromatin Dynamics
- Evolution and Genetic Dynamics
- T-cell and B-cell Immunology
- Gene Regulatory Network Analysis
- Innovative Microfluidic and Catalytic Techniques Innovation
- RNA Research and Splicing
- Mass Spectrometry Techniques and Applications
- CRISPR and Genetic Engineering
- Biomedical Text Mining and Ontologies
- Bioinformatics and Genomic Networks
Technion – Israel Institute of Technology
2016-2024
Rappaport Family Institute for Research in the Medical Sciences
2020-2023
University of Haifa
2023
Center for Systems Biology
2012-2015
Harvard University
2012-2015
Weizmann Institute of Science
2007-2011
The kinetic parameters of enzymes are key to understanding the rate and specificity most biological processes. Although specific trends frequently studied for individual enzymes, global rarely addressed. We performed an analysis k(cat) K(M) values several thousand collected from literature. found that "average enzyme" exhibits a ~0 s(-1) k(cat)/K(M) ~10(5) M(-1), much below diffusion limit characteristic textbook portrayal kinetically superior enzymes. Why do exhibit moderate catalytic...
Rubisco, probably the most abundant protein in biosphere, performs an essential part process of carbon fixation through photosynthesis thus facilitating life on earth. Despite significant effect that Rubisco has fitness plants and other photosynthetic organisms, this enzyme is known to have a remarkably low catalytic rate tendency confuse its substrate, dioxide, with oxygen. This apparent inefficiency puzzling raises questions regarding roles evolution versus biochemical constraints shaping...
Significance Almost all biological systems need to respond multiple simultaneous inputs. In yeast catabolite repression, a textbook model for signaling integration, the preferred carbohydrate glucose is thought inhibit induction of galactose genes when above threshold concentration. Instead, we show that metabolic depends on ratio and glucose. Surprisingly, critical portion information processing determines response occurs upstream canonical pathway. The use modern combinatorial approaches...
Maximizing growth and survival in the face of a complex, time-varying environment is common problem for single-celled organisms wild. When offered two different sugars as carbon sources, microorganisms first consume preferred sugar, then undergo transient delay, “diauxic lag,” while inducing genes to metabolize less sugar. This delay commonly assumed be an inevitable consequence selection maximize use Contrary this view, we found that many natural isolates Saccharomyces cerevisiae display...
The immune system plays a major role in maintaining many physiological processes the reproductive system. However, complete characterization of milieu ovary, and particularly how it is affected by female aging, still lacking. Here, we utilize single-cell RNA sequencing flow cytometry to construct description murine ovarian We show that composition cells undergoes an extensive shift with age towards adaptive immunity. analyze effect aging on gene expression chemokine cytokine networks overall...
To perform recognition, molecules must locate and specifically bind their targets within a noisy biochemical environment with many look-alikes. Molecular recognition processes, especially the induced-fit mechanism, are known to involve conformational changes. This raises basic question: Does molecular gain any advantage by such changes? By introducing simple statistical-mechanics approach, we study effect of conformation flexibility on quality processes. Our model relates specificity...
Circuit design for control of metabolism A transcriptional mechanism in yeast that allows cells to respond changes nutrient concentrations works very much like a household light-dimmer switch. That is, the system separately controls whether gene expression is “on” or “off” and extent expression. The galactose-responsive pathway activated when need switch from metabolizing glucose galactose. Ricci-Tam et al. found that, rather than using two separate elements dimmer controls, use single...
Eosinophilic esophagitis (EoE) is an allergic inflammatory condition characterized by eosinophil accumulation in the esophageal mucosa. EoE diagnosis includes a manual assessment of levels mucosal biopsies-a time-consuming, laborious task that difficult to standardize. One main challenges automating this process, like many other biopsy-based diagnostics, detecting features are small relative size biopsy.
Eosinophilic esophagitis (EoE) is an allergic inflammatory condition of the esophagus associated with elevated numbers eosinophils. Disease diagnosis and monitoring require determining concentration eosinophils in esophageal biopsies, a time-consuming, tedious somewhat subjective task currently performed by pathologists. Here, we developed machine learning pipeline to identify, quantitate diagnose EoE patients' at whole slide image level. We propose platform that combines multi-label...
Eosinophilic esophagitis (EoE) is a chronic allergic inflammatory condition of the esophagus associated with elevated esophageal eosinophils. Second only to gastroesophageal reflux disease, EoE one leading causes refractory dysphagia in adults and children. clinicopathologic disorder histological portion diagnosis requires enumerating density eosinophils biopsies, evaluating additional features such as basal zone hyperplasia helpful. However, this task time-consuming, somewhat subjective...
A multitude of cell screening assays for diagnostic and research applications rely on quantitative measurements a sample in the presence different reagent concentrations. Standard methods microtiter plates varying well density, which provide simple standardized addressability. However, testing hundreds chemical dilutions requires complex automation, typical volumes are incompatible with analysis small number cells. Here, we present microfluidic device creating high-resolution gradient...
Numerous biological functions-such as enzymatic catalysis, the immune response system, and DNA-protein regulatory network-rely on ability of molecules to specifically recognize target within a large pool similar competitors in noisy biochemical environment. Using basic framework signal detection theory, we treat molecular recognition process problem examine its overall performance. Thus, evaluate optimal properties recognizer presence competition noise. Our analysis reveals that design...
Abstract Background Extracellular feedback is an abundant module of intercellular communication networks, yet a detailed understanding its role still lacking. Here, we study interactions between polyclonal activated T cells that are mediated by IL-2 extracellular as model system. Results Using mathematical modeling show can give rise to opposite outcomes: competition or cooperation interacting cells, depending on their relative levels activation. Furthermore, the outcome interaction also...
Nutrient homeostasis—the maintenance of relatively constant internal nutrient concentrations in fluctuating external environments—is essential to the survival most organisms. Transcriptional regulation plasma membrane transporters by is typically assumed be main mechanism which homeostasis achieved. While this homeostatic we show that it does not achieve global perfect homeostasis—a condition where are completely independent for all concentrations. We criterion transporter levels must...
Metabolism underlies many important cellular decisions, such as the decisions to proliferate and differentiate, defects in metabolic signaling can lead disease aging. In addition, heterogeneity have biological consequences, differences outcomes drug susceptibilities cancer antibiotic treatments. Many approaches exist for characterizing state of a population cells, but technologies measuring metabolism at single cell level are preliminary stages limited. Here, we describe novel analysis...
Abstract Stem cells (SCs) are traditionally viewed as rare, slow-cycling that follow deterministic rules dictating their self-renewal or differentiation. It was several decades ago, when limbal epithelial SCs (LSCs) regenerate the corneal epithelium were one of first sporadic, quiescent ever discovered. However, LSC dynamics, heterogeneity and genetic signature largely unknown. Moreover, recent accumulating evidence strongly suggested actually abundant, frequently dividing display stochastic...
Maximizing growth and survival in the face of a complex, time-varying environment is common problem for single-celled organisms wild. When offered two different sugars as carbon sources, microorganisms first consume preferred sugar, then undergo transient delay, “diauxic lag”, while inducing genes to metabolize less sugar. This delay commonly assumed be an inevitable consequence selection maximize use Contrary this view, we found that many natural isolates Saccharomyces cerevisiae display...
Machine learning, and representation learning in particular, has the potential to facilitate drug discovery by screening billions of compounds. For example, a successful approach is representing molecules as graph utilizing neural networks (GNN). Yet, these approaches still require experimental measurements thousands compounds construct proper training set. While some domains it easier acquire data, others might be more limited. test on bacteria than perform vivo experiments. Thus, key...
Artificial intelligence and machine learning techniques have the promise to revolutionize field of digital pathology. However, these models demand considerable amounts data, while availability unbiased training data is limited. Synthetic images can augment existing datasets, improve validate AI algorithms. Yet, controlling exact distribution cellular features within them still challenging. One solutions harnessing conditional generative adversarial networks that take a semantic mask as an...