Prof. Masha Niv

We are intrigued by the sense of taste, and are aiming to understand how bitterness and sweetness are elicited and modified by molecules. We combine data curation (BitterDB), machine learning, ligand and structure-based drug discovery tools, cell-based functional assays and human sensory studies, to learn about the molecular recognition, structure and function of taste GPCRs.

We welcome applications from curious and enthusiastic students and postdocs.
Please consider joining our renovated beautiful lab in Rehovot.

tasty or not

Full list of publications is available here, and some glimpses to recent projects are below.

A long-standing unresolved puzzle concerns the taste of heavy water. Anecdotal evidence from the 1930s suggested that the taste of pure D2O is distinct from the neutral one of pure H2O, being described mostly as “sweet”. Next, Urey and Failla in Science (1935) concluded that, upon tasting “neither of us could detect the slightest difference between the taste of ordinary distilled water and the taste of pure heavy water”. We now clearly demonstrate that humans are able to distinguish D2O from H2O by taste, that highly purified heavy water has a distinctly sweeter taste than same-purity normal water and adds to perceived sweetness of sweeteners. In contrast, umami and bitter taste qualities are NOT enhanced by D2O, and mice are not attracted to it. The sweet taste of D2O is suppressed by lactisole, a known sweetness inhibitor of the TAS1R2/TAS1R3 sweet taste receptor, and HEK 293T cells transfected with the TAS1R2/TAS1R3 heterodimer and the chimeric Gα16gust44 G-protein are activated by D2O but not by H2O. Modeling and molecular dynamics simulations suggest internal water sites and effects on protein flexibility that may be involved in the mechanisms of receptor activation. The results of this exciting collaboration with the Jungwirth lab are now published in Communications Biology and highlighted in PNAS.

virtualscreeningfoodb

Structure reveals the activation mechanism of the MC4 receptor to initiate satiation signaling

Being constantly hungry is a daily struggle for people with genetic defects in the brain's appetite controls, and often leads to severe obesity. The Niv lab participated in a study led by Moran Shalev-Benami on the mechanism of action of the master switch for hunger in the brain: the melanocortin receptor 4, or MC4 receptor for short. In this work, now published in Science, the international team has clarified how this switch is activated by setmelanotide, a drug recently approved for the treatment of severe obesity caused by certain genetic changes. Interestingly, the findings indicate that Ca2+ is required for agonist but not antagonist efficacy. Dr. Fabrizio Fierro, a postdoc in the Niv lab, has used Molecular Dynamics simulations to show the spontaneous entry of calcium ions into the receptor binding site, both in the presence or the absence of the drug.

These results fill a gap in understanding MC4R activation and could guide the design of future weight management drugs.

Another major focus of our research program is bitter taste. There are multiple bitter taste GPCR subtypes (called T2Rs), and the number is species-specific (3 in chicken, 25 in human).

To study this complexity, we have established and expanded the BitterDB database of bitter ligands. The database currently holds information on over 1000 bitter molecules, their associated receptors in various species, SNPs in the receptors and more. There are over 23,000 users of the BitterDB worldwide.

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figure from Intense bitterness of molecules: machine learning for expediting drug discovery

Based on this information, and by gathering information also on non-bitter molecules, we have developed a machine-learning classifier, which predicts from molecules chemical structure, whether it is likely to be bitter or non-bitter. This BitterPredict tool enabled to evaluate the abundance of bitter molecules in different datasets. Specifically, it is usually assumed that bitterness signals toxicity. We applied BitterPredict to datasets of toxic molecules and found that despite common assumption, toxicity does not strongly correlate with bitterness.

toxicity does not strongly correlate with toxicity

Another point of interest relates to molecular recognition: how is it possible for a single receptor to be activated by dissimilar ligands? We found that the chemophysical characteristics, subpockets, and ligand-dependent use of interactions of the orthosteric bindings site, provide the versatility needed for accomodating multiple ligands.

Interestingly, not only does a single T2R recognize multiple bitter ligands, but a single bitter molecule can activate several T2Rs. However, bitterants that activate multiple T2Rs are not more bitter (at least not more aversive for chicken) than T2R-specific ones.

cell to beak

Because of bitter taste aversiveness, we hypothesized that might affect behavior and emotions. A significant negative effect on mood was caused by exposure to bitter-tasting mouth-rinse. Somewhat suriprisingly, the effect was asymmetric: sweet-tasting mough rinse did not elevate mood.

mood

Novel sweeteners and taste modifiers are currently under study, via integration of computational, cell-based and behavorial techniques.

kcl

The Niv lab is studying taste and smell changes due to COVID-19 infection.
Recent findings include:

Self-rated smell ability enables highly specific predictors of COVID-19 status: a case control study in Israel

But:

Tracking COVID-19 using taste and smell loss Google searches is not a reliable strategy

Masha is co-initiator and leadership team member of GCCR, THE GLOBAL CONSORTIUM FOR CHEMOSENSORY RESEARCH

More Than Smell—COVID-19 Is Associated With Severe Impairment of Smell, Taste, and Chemesthesis

Recent smell loss is the best predictor of COVID-19 among individuals with recent respiratory symptoms

Importantly, Niv and colleagues found increasing incidence of parosmia (distorted smell) and phantosmia (phantom smells) in patients recovering from COVID-19 smell loss.

lab 2019

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Curriculum Vitae

Education

PhD, Mentor: Prof. Benny Gerber (2001)
Institute of Chemistry, The Hebrew University of Jerusalem, Israel

MSc via direct PHD program (1997)
Institute of Chemistry, The Hebrew University of Jerusalem, Israel
BSc in Chemistry, cum laude (1994)
The Hebrew University of Jerusalem, Israel

Current Positions

Full Professor at The Institute of Biochemistry, Food and Nutrition

Board of Directors Member, Israel Institute for Advanced Studies (2019 - )

Board Member, Cannabinoid Research Multidisciplinary Center (2019 - )

Past Positions

Vice Dean for Research (2017- 2021)
The Robert H Smith Faculty of Agriculture, Food and Environment,
The Hebrew University of Jerusalem, Israel

Associate Professor, tenured (2014- 2021 )
Institute of Biochemistry, Food Science and Nutrition,
The Robert H Smith Faculty of Agriculture, Food and Environment,
The Hebrew University of Jerusalem, Israel

Member of cohort 5 8400 health network

"Leadership in Academia" program (2018-2019)

Director of Biochemistry and Food Science BSc study program (2014-2017)
Institute of Biochemistry, Food Science and Nutrition, The Robert H Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Israel

Visiting scholar at UCSF, hosted by Prof. Brian Shoichet (2015 summer sabbatical)

Director of MSc study program in Biochemistry and Food Science (2014-2016)
The Robert H Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Israel

Senior Lecturer (2009-2014)
The Robert H Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Israel

Lecturer (2007-2009)
The Robert H Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Israel

Post-doctoral fellow in Computational Biomedicine (2003-2007)
Weill Medical College of Cornell University, NY, US; Mentor: Prof. Harel Weinstein

Bioinformatics and Molecular Modeling Group Leader (2000-2003)
Keryx Biopharmaceuticals, Jerusalem, Israel

Teaching

Introduction to Bioinformatics and Structural Biochemistry (71437)

Methodology of Sensory Food Evaluation (71451)

Laboratory in Sensory Food Evaluation (71450)

Selected Topics in Structure And Function of GPCR- 71136

Distinctions and Awards

Vigevani Visiting Professor to Italy (2017-2018)

Women’s League for Israel Senior Lectureship in Nutrition (since 2011)

Krill Prize for Excellence in Science from the Wolf Foundation (2010)

Fritz Haber research award (1999)

BSc honorary award (1993)

DAAD scholarship (1992)

Faculty of science dean`s list (1991)

Elwing award for excellence in analytical chemistry (1991)

Recent international conferences

Keynote "Bitter and sweet molecules and receptors: insights from integrating modeling and experiment"
European Chemosensory Research Organization (ECRO) in Berlin, Germany (2022)

"The Taste of Drugs and Food - Learning with Big (and Small) Data" Computational Chemistry GRC, Spain (2022)

“Predicting and modulating bitterness” Industry Symposium at ACHEMS meeting (2022 - Florida US, hybrid)

Keynote “Taste receptors and their ligands” First Transatlantic ECI conference (2021 - virtual)

i-GPCRnet consortium on ‘G protein-coupled receptors – from physiology to drugs’ (2021 - virtual)

“Taste, drugs and toxicity”, FISEB/Ilanit – invited talk in Drug Discovery session, Eilat, Israel (2020)

“Applying data science methods to taste: what have we learned and challenges ahead”
International Symposium on Olfaction and Taste (ISOT) (2020)

34th Bitter or not? Predicting and monitoring taste in health and disease EFFoST 2020 /

“Taste and nutrition, with a little help from big data” Future of Health, Tel Aviv, Israel (2019)

Pangborn Sensory Symposium, Edinburgh, Scotland (2019)

ECRO Wurzburg, Germany (2018)

Dechema BIOFLAVOUR Biotechnology of Flavours, Frankfurt, Germany (2018)

Weurman Flavour Research Symposium, Graz, Austria (2017)

ECRO meeting, Cambridge, UK (2017)

Pangborn Sensory Science Symposium, Rhode Island, USA (2017)

GLISTEN COST CM1027, Prague, Czech Republic, invited (2016)

ECRO meeting, Athens, Greece, invited (2016)

EupFI Lisbon, Portugal, invited (2016)

EuroQSAR, Verona, Italy, Keynote (2016)

ISQPB President’s meeting, Bergen, Norway, Keynote, declined (2016)

ACHEMS annual meeting, Florida, US, invited (2015)

3DSig Boston, US, Keynote (2014)

Nauta GPCR Medicinal Chemistry Symposium, Amsterdam, Netherlands, invited (2013)

Cecam workshop, Lausanne, Switzerland, invited (2012)

ISQPB President’s meeting, Cetraro, Italy, invited (2010)

Academic Activities

Editorial board member, Chemical Senses, OUP (2020-)
Advisory board member for ScienceAbroad (2017- )

Editorial Advisory Board Member (2015-2017)
Journal of Agricultural and Food Chemistry

Editorial Board Member (2014- )
Scientific Reports, Nature publishing group

SAB member for international PhD school (Bavaria)

Academic chair of Food Innovation Forum, Israel (2016- )

Member of Fritz Haber Center for Molecular Dynamics (2012- )

Member of Jerusalem Brain Community (2016- )

Management committee member and WG leader in COST ACTION CM1027 (GLISTEN) (2013- )

Management committee substitute member in COST ACTION CA15135 (Mu.Ta.Lig) (2016- )

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List of Publications

Google Scholar Profile

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Lab Members

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DR. EINAV MALACH
Lab Technician

Dr. Einav Malach

Lab Technician

einav.cohen@mail.huji.ac.il

Research Interests:

Taste receptor activation, post-stimulation with sweet and bitter compounds.

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ASA TIROSH

PhD Student

Asa Tirosh

PhD Student

Research Interests:

Implementing taste receptors in cell-based assays on new cell line
Cloning mutations in bitter taste receptors

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NITZAN DALLAL

MSc Student

Nitzan Dallal

MSc Student

Research Interests:

Investigate bitter taste receptors in cell-based assays

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GIL DANIEL

MSc Student

Gil Daniel

MSc Student

Research Interests:

Cell based research of sweet taste receptors

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LIOR PERI

MSc Student

Lior Peri

PhD Student

lior.peri@mail.huji.ac.il

Research Interests:

Taste receptor activation, post-stimulation.
Sensory analysis of tastants.

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SHIR EYAL

Amirim Undergraduate

Shir Eyal

Amirim Undergraduate

Research Interests:

Bitter taste receptors activation and signaling in cell-based assays

tomer green

TOMER GREEN

MSc student

Tomer Green

MSc student

tom3rg@gmail.com

Research Interests:

Using machine learning to study and analyze taste perception and molecules Using data mining to understand customer taste priorities)

sharon

SHARON ZARFATI

MSc student

Sharon Zarfati

MSc student

Research Interests:

Investigate taste receptors in cell-based assays
Identify new ligands for taste receptors

Moran

MORAN DAVID

MSc student

Moran David

MSc student

Research Interests:

Computational research of sweet taste receptors

Noga

NOGA NIR

MSc student

Noga Nir

MSc student

Research Interests:

Bitter taste receptors activation and signaling in cell-based assays

Alon

ALON RAINISH

MSc student

Alon Rainish

MSc student

Research Interests:

Structure and ligand based drug discovery for bitter taste receptors

EVGENII ZIAIKIN

PhD student

Evgenii Ziaikin

PhD student

Research Interests:

Chemoinformatics of taste

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Alumni

Lab alumni hold positions in the field of computational or food science, working in The Ministry of Health, Evogene, Biomica, BiomX, Mobileye, Miloubar and more, or work in academia (i.e. UCSF, TUM).

Name	Project(s)	Degree in the lab	Current position
Nitzan Dubovski	Effects of bitter and sweet taste compounds on mood and behavior; Molecular interactions of sweet and bitter compounds with their target receptors.	PhD Student	Dr., in Biolojic Design
Yaron Ben Shoshan Galetzki			Dr., in stealth mode startup company
Natalie Ben Abu	Phenotype-genotype interaction in taste: sensory analysis of taste mixtures by a genotyped human panel; Bitter tastants, sugars and salts, and the effect of different mixtures on the taste intensity.	PhD Student	Dr., in DouxMatok
Dr. Fabrizio Fierro	Computational characterization of GPCR/ligand interaction at the molecular level; Effect of amino acids substitution on protein function through bioinformatics tools and MD simulations.	Post-doctoral fellow	Protai
Eitan Margulis	Machine learning applications for taste prediction; Chemoinformatic research and analysis of odorants and bitter taste molecules	PhD Student	Dr., in Anima Biotech
Marina Shudler	Kinase dynamics	MSc	Software developer in Tower Watson, UK
Dr. Shu Cheng	Kinase dynamics	Postdoctoral fellow	Postdoc in the US
Dr. Noga Kowalsman	Molecular recognition in GPCRs	Postdoctoral fellow	Bioinformatician and structural computational biologist at BiomX LTD
Yonatan Aisner	Thioredoxin mimetic peptides	Undergrad	Graduated
Anat Levit	Molecular recognition in GPCRs, bitter taste	PhD	Postdoc in UCSF
Morin Shavro	Kinase dynamics	MSc	Software developer, Prodware
Ayana Wiener	BitterDB, BitterPredict	PhD	MobilEye
Dr. Avi Ben-Shimon	Peptides dynamics and design	Postdoctoral fellow	Independent consultant
Nitzan Sharabi	Ligand-based virtual screening	Amirim Undergraduate	Ministry of Health
Maria Verbov	Bitter taste recognition	MSc	Davidson Institute, WIS
Mazi Elyahu	Bitterness and toxicity	MSc, non-research	Graduated
Lizi Hazan	Bitter taste of peptides	Amirim Undergraduate	MSc at WIS
Shira Cheled-Shoval	Bitter recognition by chicken receptors	PhD (joint with Prof. Uni)	Head of Nutrition R&D Department at Miloubar
Dr. Michal Slutzki	Protein-protein interactions	Postdoctoral fellow	Computational Product Developer at Evogene
Daniel Taieb	Peptide folding and docking	Undergrad	Graduated
Nitzan Cohen-Amin	Effects of bitter and sweet taste on mood	MSc	PhD student in the lab
Dr. Malkeet Singh	Molecular recognition in GPCRs, bitter taste	Postdoctoral fellow	Postdoc in Bar Ilan University
Ava Xue	Phylogenetic analysis of taste receptors	MSc	PhD at BIU
Yaron Ben Shoshan-Galeczki	The sweet taste receptor	MSc	PhD student in the lab
Natalie Ben Abu	Sensory analysis of sugars and salts	MSc	PhD student in the lab
Antonella Di Pizio	Bittertaste receptors	Postdoctoral fellow	Junior PI at the Technical University of Munich
Ido Nissim	Bitter taste and toxicity	MSc	Senior Data Engineer at StoreMaven
Tamir Dingjan	T2R14	Postdoctoral fellow	Postdoctoral fellow at WIS
Kim Asseo	Sensory nutrition and COVID-19	MSc	Data Analyst at AiDock
Hadar Klein	Sensory analysis of taste mixtures	MSc	Dietitian and PHD student at BGU
Yaron Ben Shoshan Galezcki	The role of chirality in sweetness perception GPCR class C receptor; the sweet taste receptor, modeling, docking and activation	PhD	at a Biotech company