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Head of Institute: Prof. Oren Tirosh

Administrative manager: Rakefet Kalev

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Institute of Biochemistry, Food Science and Nutrition,
Robert H. Smith Faculty of Agriculture, Food and Environment,
The Hebrew University of Jerusalem, 
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Forbes, J. ; Bissoyi, A. ; Eickhoff, L. ; Reicher, N. ; Hansen, T. ; Bon, C. G. ; Walker, V. K. ; Koop, T. ; Rudich, Y. ; Braslavsky, I. ; et al. Water-organizing motif continuity is critical for potent ice nucleation protein activity. 2022, 13, 5019. Publisher's VersionAbstract
Bacterial ice nucleation proteins (INPs) can cause frost damage to plants by nucleating ice formation at high sub-zero temperatures. Modeling of Pseudomonas borealis INP by AlphaFold suggests that the central domain of 65 tandem sixteen-residue repeats forms a beta-solenoid with arrays of outward-pointing threonines and tyrosines, which may organize water molecules into an ice-like pattern. Here we report that mutating some of these residues in a central segment of P. borealis INP, expressed in Escherichia coli, decreases ice nucleation activity more than the section’s deletion. Insertion of a bulky domain has the same effect, indicating that the continuity of the water-organizing repeats is critical for optimal activity. The ~10 C-terminal coils differ from the other 55 coils in being more basic and lacking water-organizing motifs; deletion of this region eliminates INP activity. We show through sequence modifications how arrays of conserved motifs form the large ice-nucleating surface required for potency.
Veltman, B. ; Harpaz, D. ; Melamed, S. ; Tietel, Z. ; Tsror, L. ; Eltzov, E. Whole-cell bacterial biosensor for volatile detection from Pectobacterium-infected potatoes enables early identification of potato tuber soft rot disease. 2022, 247, 123545. Publisher's VersionAbstract
Half of the harvested food is lost due to rots caused by microorganisms. Plants emit various volatile organic compounds (VOCs) into their surrounding environment, and the VOC profiles of healthy crops are altered upon infection. In this study, a whole-cell bacterial biosensor was used for the early identification of potato tuber soft rot disease caused by the pectinolytic bacteria Pectobacterium in potato tubers. The detection is based on monitoring the luminescent responses of the bacteria panel to changes in the VOC profile following inoculation. First, gas chromatography-mass spectrometry (GC-MS) was used to specify the differences between the VOC patterns of the inoculated and non-inoculated potato tubers during early infection. Five VOCs were identified, 1-octanol, phenylethyl alcohol, 2-ethyl hexanol, nonanal, and 1-octen-3-ol. Then, the infection was detected by the bioreporter bacterial panel, firstly measured in a 96-well plate in solution, and then also tested in potato plugs and validated in whole tubers. Examination of the bacterial panel responses showed an extensive cytotoxic effect over the testing period, as seen by the elevated induction factor (IF) values in the bacterial strain TV1061 after exposure to both potato plugs and whole tubers. Moreover, quorum sensing influences were also observed by the elevated IF values in the bacterial strain K802NR. The developed whole-cell biosensor system based on bacterial detection will allow more efficient crop management during postharvest, storage, and transport of crops, to reduce food losses.
Dubovski, N. ; Fierro, F. ; Margulis, E. ; Ben Shoshan-Galeczki, Y. ; Peri, L. ; Niv, M. Y. Taste GPCRs and their ligands. In Progress in Molecular Biology and Translational Science; Progress in Molecular Biology and Translational Science; Academic Press, 2022. Publisher's VersionAbstract
Taste GPCRs are expressed in taste buds on the tongue and play a key role in food choice and consumption. They are also expressed extra-orally, with various physiological roles that are currently under study. Unraveling the roles of these receptors relies on the knowledge of their ligands. Combining sensory, cell-based and computational approaches enabled the discovery of numerous agonists and several antagonists. Here we provide a short overview of taste receptor families, main recent methods for ligands discovery, and current sources of information about known ligands. The future directions that are likely to impact the taste GPCR field include focus on ligand interactions with naturally occurring polymorphisms, as well as harnessing the power of CryoEM and of multiple signaling readout techniques.
Asseo, K. ; Niv, M. Y. Harnessing Food Product Reviews for Personalizing Sweetness Levels. Foods 2022, 11. Publisher's VersionAbstract
Sweet taste is innately appealing, ensuring that mammals are attracted to the sweetness of mother’s milk and other sources of carbohydrates and calories. In the modern world, the availability of sugars and sweeteners and the eagerness of the food industry to maximize palatability, result in an abundance of sweet food products, which poses a major health challenge. The aim of the current study is to analyze sweetness levels, liking, and ingredients of online reviews of food products, in order to obtain insights into sensory nutrition and to identify new opportunities for reconciling the palatability–healthiness tension. We collected over 200,000 reviews of  30,000 products on Amazon dated from 2002 to 2012 and  350,000 reviews of  2400 products on iHerb from 2006 to 2021. The reviews were classified and analyzed using manual curation, natural language processing, and machine learning. In total,  32,000 (Amazon) and  29,000 (iHerb) of these reviews mention sweetness, with 2200 and 4600 reviews referring to the purchased products as oversweet. Oversweet reviews were dispersed among consumers. Products that included sucralose had more oversweet reviews than average. 26 products had at least 50 reviews for which at least 10% were oversweet. For these products, the average liking by consumers reporting oversweetness was significantly lower (by 0.9 stars on average on a 1 to 5 stars scale) than by the rest of the consumers. In summary, oversweetness appears in 7–16% of the sweetness-related reviews and is less liked, which suggests an opportunity for customized products with reduced sweetness. These products will be simultaneously healthier and tastier for a substantial subgroup of customers and will benefit the manufacturer by expanding the products’ target audience. Analysis of consumers’ reviews of marketed food products offers new ways to obtain informative sensory data.
Hintschich, C. A. ; Niv, M. Y. ; Hummel, T. The taste of the pandemic—contemporary review on the current state of research on gustation in coronavirus disease 2019 (COVID-19). International Forum of Allergy & RhinologyInternational Forum of Allergy & RhinologyInt Forum Allergy Rhinol. 2022, 12, 210 - 216. Publisher's VersionAbstract
Abstract Subjectively perceived impairment of taste is a common and distinct symptom of coronavirus disease 2019 (COVID-19). Large meta-analyses identified this symptom in approximately 50% of cases. However, this high prevalence is not supported by blinded and validated psychophysical gustatory testing, which showed a much lower prevalence in up to 26% of patients. This discrepancy may be due to misinterpretation of impaired retronasal olfaction as gustatory dysfunction. In addition, we hypothesized that COVID-19?associated hyposmia is involved in the decrease of gustatory function, as found for hyposmia of different origin. This indirect mechanism would be based on the central-nervous mutual amplification between the chemical senses, which fails in COVID-19?associated olfactory loss. However, further research is necessary on how severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) may directly impair the gustatory pathway as well as its subjective perception.
Goldberg, D. ; Charni-Natan, M. ; Buchshtab, N. ; Bar-Shimon, M. ; Goldstein, I. Hormone-controlled cooperative binding of transcription factors drives synergistic induction of fasting-regulated genes. Nucleic Acids Res 2022, gkac358. Publisher's VersionAbstract
During fasting, hepatocytes produce glucose in response to hormonal signals. Glucagon and glucocorticoids are principal fasting hormones that cooperate in regulating glucose production via gluconeogenesis. However, how these hormone signals are integrated and interpreted to a biological output is unknown. Here, we use genome-wide profiling of gene expression, enhancer dynamics and transcription factor (TF) binding in primary mouse hepatocytes to uncover the mode of cooperation between glucagon and glucocorticoids. We found that compared to a single treatment with each hormone, a dual treatment directs hepatocytes to a pro-gluconeogenic gene program by synergistically inducing gluconeogenic genes. The cooperative mechanism driving synergistic gene expression is based on ‘assisted loading’ whereby a glucagon-activated TF (cAMP responsive element binding protein; CREB) leads to enhancer activation which facilitates binding of the glucocorticoid receptor (GR) upon glucocorticoid stimulation. Glucagon does not only activate single enhancers but also activates enhancer clusters, thereby assisting the loading of GR also across enhancer units within the cluster. In summary, we show that cells integrate extracellular signals by an enhancer-specific mechanism: one hormone-activated TF activates enhancers, thereby assisting the loading of a TF stimulated by a second hormone, leading to synergistic gene induction and a tailored transcriptional response to fasting.