Prof. Masha Niv

During COVID-19 pandemic, the Niv lab is studying taste and smell changes:

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

The research is ongoing, please share our survey https://gcchemosensr.org/surveys/ or participate in it in the language of your choice, if you were sick in the last 2 weeks.

 

 

We are intrigued by the sense of taste, and are aiming to understand how bitterness and sweetness are elicited and modified by molecules.

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 https://www.nature.com/articles/s42003-021-01964-y and highlighted in PNAS https://blog.pnas.org/2021/04/heavy-water-tastes-sweeter/

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.

mc4

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.

 

niv-reformulation

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

lab 2019

 

 

 

 

See also: Masha_Niv

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

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

  • 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

 

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

 

  • “Taste, drugs and toxicity”, FISEB/Ilanit – invited talk in Drug Discovery session, Eilat, Israel (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 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)
  • Management committee member and WG leader in COST ACTION CM1027 (GLISTEN) (2013- )
  • Management committee substitute member in COST ACTION CA15135 (Mu.Ta.Lig) (2016- )

 

See also: Masha_Niv

List of Publications

See also: Masha_Niv

Lab Members

einav
See also: Masha_Niv

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.

nitzan
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NITZAN DUBOVSKI

PhD Student


Nitzan Dubovski

PhD Student

nitzan.dubovski@mail.huji.ac.il

Research Interests:

  • Effects of bitter and sweet taste compounds on mood and behavior.

  • Molecular interactions of sweet and bitter compounds with their target receptors.

eitan
See also: Masha_Niv

EITAN MARGULIS

MSc Student


Eitan Margulis

PhD Student

Eitan.Margulis@mail.huji.ac.il

Research Interests:

  • Machine learning applications for taste prediction

  • Chemoinformatic research and analysis of odorants and bitter taste molecules

yaron
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YARON BEN SHOSHAN-GALECZKI

PhD Student


Yaron Ben Shoshan-Galeczki

PhD Student

yaron.benshosan@mail.huji.ac.il

Research Interests:

  • How can L-Glucose elicit sweet taste sensation? The role of chirality in sweetness perception.

  • GPCR class C receptor; the sweet taste receptor, modelling, docking and activation.

hadarb
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HADAR KLEIN

MSc Student


Hadar Klein

MSc Student

hadarbreen@gmail.com

Research Interests:

  • Studying of sweet taste mechanisms: Sensory analysis of taste mixtures.

 

smallnatalie
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NATALIE BEN ABU

PhD Student


Natalie Ben Abu

PhD Student

natalie.smolinsky@mail.huji.ac.il

Research Interests:

  • 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.

lior
See also: Masha_Niv

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.

fabrizio fierro
FABRIZIO FIERRO

Post-doctoral fellow

Fabrizio Fierro


Post-doctoral fellow  


fabriz.fierro@gmail.com

Research Interests:

  • Computational characterization of GPCR/ligand interaction at the molecular level.
  • Effect of amino acids substitution on protein function through bioinformatics tools and MD simulations.

kim asseo

KIM ASSEO

MSc student

Kim Asseo

MSc student

kim.asseo@gmail.com

Research Interests:

  • Sensory nutrition and COVID-19 – data analysis of taste and smell responses

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)
dor marcusDOR MARCUS

MSc student

Dor Marcus

 

MSc student

 

Dormarcus18@gmail.com

Research interests:

  • taste receptor activation
  •  sensory analysis of sweet tastants

hodaya krabi
HODAYA KRABI

MSc student

Hodaya Krabi

MSc student

hodaya.karbi@weizmann.ac.il

Research interests:

  • Studying ligand-receptor interactions in sensory GPCRs

 

See also: Masha_Niv

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

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

Computational chemist at HepRx 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

Bitter recognition by chicken receptors

PhD (joint  with Prof. Uni)

Graduating in 2016

Dr. Michal Slutzki

Protein-protein interactions

Postdoctoral fellow

Computational scientist, FuturX Biotech Accelerator

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

Dr. Shira Cheled-Shoval

Taste perception mechanisms in chickens’

PhD

Graduated

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

Yandex data scientist

Tamir Dingjan

T2R14

Postdoctoral fellow

Postdoctoral fellow at WIS

 

 

See also: Masha_Niv

Media

March 2021

חוקרות קורונה

תרופות מרות

GPCR Podcast - Bitter or sweet, that is the question

Coverage in Hebrew on our research on taste and smell loss in COVID-19

Coverage in Hebrew on long term symptoms, including smell and taste loss, in COVID-19

Coverage in English and other languages on our research on taste and smell loss in COVID-19

 

Dr. Fabrizio Fierro, Post-Doctoral Fellow

HUJI researchers develop an algorithm that shortens the search for healthy sweeteners (Hebrew)

Article on Masha and Avner Niv at Jerusalem Brain Week in Makor Rishon Weekend Magazine (Hebrew)

Eat well to age well,  Paris - November 2018

Antonella won a JBC travel grant for presenting at a Keystone Symposia, February 2018 (English)

BitterPredict article on PNAS Blog, October 2017 (English)

Radio interview on bitter and sweet research, October 2017 (Hebrew)

BitterPredict article on Ynet, October 2017 (Hebrew)

Exhibition on sugar, October 2017 (Hebrew)

Talk: “The Taste of Poisons and of Therapeutic Drugs: Who Cares and How to Predict it”, September 2017 (English)

Food design exhibition, March 2016 (Hebrew)

Recorded Talks

Bitter taste GPCRs and their ligands

Prof. Masha Niv

masha-talk1
https://www.youtube.com/watch?v=8y6wbzVIObg"

Finding the sweet spot: modeling GPCRs and discovery of sweet compounds

Yaron Ben-Shoshan Galeczki

yaron galeczi talk
https://www.youtube.com/watch?v=fld2rOujjp0

 

See also: Masha_Niv

Photo Gallery

brunch1
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brunch2
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brunch3
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brunch4
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brunch5
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palmachim1
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labverenafarewelljuly2019 Sophie purim

 

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Supplementary Information

Data from papers 

See also: Masha_Niv, research