17 innovations from Bar-Ilan University, available for licensing, co-investment, or spin-out through BIRAD.
Cohen Haim
Aging is associated with detrimental changes in chromatin structure and gene expression, contributing to inflammation, metabolic decline and tissue dysfunction. SIRT6, a histone deacetylase, plays a key role in maintaining chromatin integrity and promoting longevity. Here, we characterized age-related changes in chromatin accessibility in the murine liver. We found that aging leads to increased chromatin accessibility. These changes were accompanied by upregulation of inflammation-related pathways and downregulation of metabolic pathways. Remarkably, SIRT6 overexpression reversed these changes, reducing inflammation and enhancing metabolic function. Notably, ETS family members were enriched in regions with increased accessibility during aging, while liver-enriched transcription factors (LETFs) were enriched in regions with reduced accessibility. H3K9ac and H3K56ac ChIP-seq analyses showed that H3K9ac, but not H3K56ac, is associated with increased accessibility during aging and that SIRT6 can reverse this effect. Furthermore, an viral system of AAV-mediated SIRT6 overexpression experiment in aged mice demonstrated that SIRT6 not only slows age-related chromatin changes but can also reverse them, rejuvenating chromatin accessibility to a youthful state. This highlights the potential of SIRT6 based therapy to rejuvenate aged tissues and mitigate age-related dysfunction.
alon shahar
We present a method for multiplexed RNA and protein detection in intact, thick organoids. Organoid thickness represents a major barrier to in situ molecular analysis. Our approach extends Expansion Sequencing (ExSeq)—previously limited to tissue sections up to ~50 µm—to organoids ranging from 100 µm to 300 µm in diameter. Importantly, organoids exceeding 300–500 µm frequently develop necrotic cores due to restricted oxygen and reagent diffusion, making 300 µm a practical upper limit for intact, physiologically relevant analysis. A key innovation of this method is delayed hydrogel polymerization, which enables uniform diffusion of gel monomers throughout the tissue prior to crosslinking. Additional challenges, including limited surface area, enzyme penetration, and imaging depth, were addressed through automated pipetting, glass-slide embedding, and protocol optimizations (Table). By physically expanding whole brain organoids within a hydrogel matrix, this method enhances spatial resolution by up to ~10× and allows iterative rounds of antibody staining and in situ RNA sequencing in the same sample. While demonstrated in neurodevelopmental organoid models such as STXBP1 encephalopathy, this platform is broadly applicable to diverse organoid systems for 3D multimodal molecular profiling.
Popovtzer Rachala
The human microbiome is emerging as a central player in health and disease. In particular, a strong connection has been shown between the human gut microbiome population and the etiology of a variety of diseases, ranging from gastrointestinal diseases to cancer, cardiovascular disease, and brain disorders. A fundamental phenomenon of bacterial communication is quorum sensing, in which signal molecules, termed autoinducers (AI), regulate bacterial colony density and coordinate pathogenic behaviors. AI molecules are emerging as important factors, and key indicators, in various diseases. However, despite their importance, there has not yet been developed a sensitive and reliable sensor that can detect AI communication molecules in real-time, for early diagnosis and monitoring of disease. The present project aims to develop an innovative biochip technology, combining advanced synthetic biology together with cutting-edge electronic systems, for quantitative, sensitive, and real-time detection of AI signals for diagnosis of gastrointestinal diseases. Our technology consists of a nano biochip, incorporating a variety of synthetic bacteria each engineered to sense a specific disease-associated AI molecule and generate a quantifiable electric signal in response, which will be measured, and wirelessly transmitted, by the electronic component. The nano biochip will accurately associate a specific electric response with a specific AI type. The ability of the nano-biochip system to identify the specific AI signals will be investigated in bacterial conditioned media and in ex vivo samples from gastrointestinal disease patients at different stages of the disease. This novel technology has the potential to serve as a next-generation tool for non-invasive early diagnosis, staging, and monitoring of gastrointestinal diseases. The nanobiochip’s unique features will also advance the potential for real-time detection of gastrointestinal disorders within the human body.
Cohen Haim
To explore the role of protein post-translational modifications on lifespan and healthspan , we developed the PHARAOH computational tool based on the 100-fold differences in longevity within the mammalian class. Analyzing acetylome/phosphorylome and proteome data across 107 mammalian species identified 482 and 695 significant longevity-associated acetylated lysine residues in mice and humans, respectively. In addition, we have recognized 2115 longevity associated p phosphorylations. In regards to acetylations, these sites include acetylated lysines in short-lived mammals that were replaced by permanent acetylation or deacetylation mimickers, glutamine or arginine, respectively, in long-lived mammals. Conversely, glutamine or arginine residues in short-lived mammals were replaced by reversibly acetylated lysine in long-lived mammals. For phosphorylations, site these sites include phosphorylated Serine (S), Tyrosine (Y) and threonine (T) or their replacement to aspartic acid (D) or glutamic acid (E)or Alanine (A) and Y to phenylalanine (Y to F). Pathway analyses of the acetylation sites highlighted the involvement of mitochondrial translation, cell cycle, fatty acid oxidation, transsulfuration, DNA repair and others in longevity. A validation assay showed that substitution of lysine 386 with arginine in mouse cystathionine beta synthase, to attain the human sequence, increased the pro-longevity activity of this enzyme. Likewise, replacing the human ubiquitin-specific peptidase 10 acetylated lysine 714 with arginine as in short-lived mammals, reduced its anti-neoplastic function. These findings provide a computational tool for identifying modifications that control longer healthy life and potential interventions to extend human healthspan.
Levanon Erez
system to design guides for selected gene targeting by the ADAR enzyme
