MIT’s Center for Biomedical Innovation has entered into a sponsored research agreement with The Coca-Cola Company to support collaborative research projects in science and engineering that can develop fundamental understandings and technologies for helping to uncover new sweetening solutions.

MIT principal investigators (PIs) are invited to form collaborations with other top research teams from around the world in order to develop innovative proposals. Funding from The Coca-Cola Company will be awarded by a Joint Steering Committee to projects selected through a request for proposals.

Coca-Cola has identified that consumers around the world increasingly value drinks that taste great but have less sugar and fewer calories. With a history of innovation in this area, the company seeks to ensure it continues to deliver beverages that maintain a sugar-like taste with reduced or zero calories.

The long-term vision of this challenge is to discover appealing taste solutions that offer the full taste of sugar without the calories. Because the complexity of this challenge involves not just capturing sweetness, but replicating the full taste profile of sugar, we encourage innovative thinking that goes beyond current technologies.

Alternative sugar solutions may ultimately involve novel sweeteners, unique ingredient combinations, or inventive ways of delivering a sugar-like taste experience. Successful solutions will need to be safe, scalable, affordable, and compatible with foods and beverages.

The Grand Challenge is searching for interdisciplinary projects that could advance scientific understanding of sweet taste, that could uncover novel ways for improving sweet taste quality, and that could lead to game-changing sweetening solutions.

Proposals are expected to fall into 4 areas, but additional innovative areas will be considered:

• Advancing the science of taste and aroma and filling in key knowledge gaps in the biology and neuroscience of sweet taste perception and sweet taste quality, such as identifying the physiological mechanisms that distinguish sugar from other sweeteners.
• Tools and assay technologies to screen sweetness beyond current technologies (especially HTP methods for assessing the quality of sweetness rather than just sweet intensity).
• Advanced chemical approaches for studying, creating, or delivering superior sweet taste quality (e.g., novel research methods, molecular tools for probing the biological mechanisms, combinatorial chemistry (peptides, glycans, etc.), or delivery systems).
• Machine learning and AI for the analysis of complex data sets related to taste perception and for revealing hidden correlations around taste interactions.

We know that great ideas can come from a variety of people and places. A key feature of this Grand Challenge is to bring about game-changing ideas and catalyze discovery by bringing interdisciplinary teams together. Therefore, we encourage participation from the entire MIT academic community and beyond.

This can include undergraduates, graduate students, post-graduates as well as academic researchers from a variety of fields or other institutions. Nevertheless, each proposal must be led by an MIT principal investigator (PI), with investigators from other institutions allowed and encouraged to collaborate with an MIT investigator. No individual should be a lead PI on more than one proposal.

• Proposal deadline: May 29, 2024
• Review and selection process: June - July
• Earliest start date: September 1, 2024

Research proposals for the Grand Challenge will be reviewed by a Joint Steering Committee (JSC) composed jointly of members from MIT faculty and The Coca-Cola Company R&D team. To be considered, research proposals will need to follow some limited guiding criteria.

As solutions may be diverse and may include concepts beyond additive ingredients, all proposals should connect the proposed research to how it will find or will help find new alternatives to sugar. Each proposal should lay out not only the work required for finding a solution, but also the overall rationale, approaches for developing a solution, and the existing tools or those that will need to be developed for the work.

Criteria for research methods:

• All research must adhere to MIT research policies (Research Policies and Procedures | MIT Office of the Vice President for Research), with the following exceptions:
• Experimentation on animals or animal tissues is not permitted, but use of previously developed animal cell culture models is permitted.
• Experimentation with human-derived embryonic cells is not permitted.
• Compliant with FDA and MIT human research policies and protections.
• Compliant with The Coca-Cola Company’s Guiding Principles for Funding Scientific Research.

The Coca-Cola Company continues to invest in internal and external research in this area, and it is possible that company is currently or will in the future be investing in same or similar technology as disclosed in the research proposals submitted in this Grand Challenge. Participants acknowledge that The Coca-Cola Company has the right to consider same or similar technology from third parties.

The 2024 Request for Proposals will fund and support up to two large interdisciplinary projects and, potentially, smaller seed projects.

Recommendation: A project duration of 2 years or less. Shorter exploratory projects that are 1 year in duration are encouraged and may be eligible for additional funding upon completion.

The total amount available for the first year of the approved Proposals is expected to be at least $1.0 million, inclusive of indirect costs.

The Joint Steering Committee (JSC) will evaluate and make a determination regarding recommendations for which Proposals should be developed into a full Research Project Plan by July 1, 2024.

The Research Project Plan will include parts of the proposal (a description of the scope of work and research activities, decision points, and budget), as well as finalized milestones and a payment schedule, which the project teams will jointly finalize with CBI staff and the sponsor. Commitment to project funding is made at execution of the Research Project Agreement and is contingent on final approval of a Research Project Plan. The earliest planned execution date for Project Agreement is July 15, 2024.

Please feel free to reach out to cbi@mit.edu with any questions.

Application should be submitted via the MIT principal investigator’s (PI) academic department. Instructions for applying can be found here.

The Coca-Cola Company has provided the following statement regarding its scientific interests as they relate to this sponsored program, and researchers are encouraged to review the company's scientific research principles. The views expressed here do not represent those of MIT, the Center for Biomedical Innovation, or the individual researchers whose projects may be funded under this program.

The Coca-Cola Company wants to give consumers great-tasting choices with fewer or no calories. We support the current recommendations of several leading health authorities that individuals should not consume more than 10% of their total calories from added sugar. We are taking action on reducing added sugar even where it means changes to our most popular, time-tested products - putting our strength in innovation to meet our consumers’ evolving needs. The goal of these efforts is to give people the low and no-sugar drinks they want without having to give up the great tastes they know and love.

Providing sugar-like taste while removing sugar is a grand challenge. Sweeteners are often several hundred times sweeter than sugar and can replace sugar in foods and drinks to give you a sweet taste with few or no calories. While there are more than a hundred known natural molecules and numerous synthetic compounds that are sweet to humans (1), only sugars provide sugar-like taste. We believe there are more yet to be discovered alternatives to sugar solutions that will offer sweetness with sugar-like taste.

Replicating sugar-like taste is about taste quality. Among the notable taste quality differences reported between sugars and sugar alternatives are: (a) intensity response profiles (which as often linear for sugars but non-linear for sugar alternatives with increased concentrations), (b) temporal profiles (such as variable onset and extinction of sweetness), (c) off taste (such as bitter, metallic, or licorice notes), (d) adaptation behaviors (such as decreased sweet intensity detection upon repeated sipping), and (e) mouthfeel (tactile sensation such as sugar-like syrupiness) (2). These and other taste qualities for replacing sugar are central to this Grand Challenge. When developing proposals related to the 4 areas of interest, researchers should address how such research will improve taste quality and help find solutions that provide superior alternatives to what are available.

Sugar-like taste is only a part of this Grand Challenge. There are additional criteria that will be needed after identifying new alternatives to sugar solutions. Importantly, these solutions will need to be safe to consume & not harm health. They will also need to be stable and possess physiochemical properties compatible for use and when producing ready to consume foods and beverages. Successful alternatives, as well as the methods for producing them, should be viewed as natural, environmentally friendly, and have the potential to be scalable so as to fit the needs of the food and beverage industry and consumers. We recognize that many of these characteristics cannot be predicted before the solutions are discovered. Rather, we are providing these criteria so researchers can understand the scope of this Grand Challenge and the criteria needed for a successful alternative to sugar. Nevertheless, proposed solutions able to address these criteria are encouraged.

Taste Physiology

• Ahmad R, Dalziel JE. G Protein-Coupled Receptors in Taste Physiology and Pharmacology. Front Pharmacol. 2020 Nov 30;11:587664.
• Chaudhari N, Roper SD. The cell biology of taste. J Cell Biol. 2010 Aug 9;190(3):285-96. doi: 10.1083/jcb.201003144. Erratum in: J Cell Biol. 2010 Oct 18;191(2):429.
• Doyle ME, Premathilake HU, Yao Q, Mazucanti CH, Egan JM. Physiology of the tongue with emphasis on taste transduction. .Physiol Rev. 2023 Apr 1;103(2):1193-1246.
• Ohla K, Yoshida R, Roper SD, Di Lorenzo PM, Victor JD, Boughter JD, Fletcher M, Katz DB, Chaudhari N. Recognizing Taste: Coding Patterns Along the Neural Axis in Mammals. Chem Senses. 2019 Apr 15;44(4):237-247.
• Taruno A, Nomura K, Kusakizako T, Ma Z, Nureki O, Foskett JK. Taste transduction and channel synapses in taste buds. Pflugers Arch. 2021 Jan;473(1):3-13.

Sweet Taste Detection

• Nelson G, Hoon MA, Chandrashekar J, Zhang Y, Ryba NJ, Zuker CS. Mammalian sweet taste receptors. Cell. 2001 Aug 10;106(3):381-90.
• Li X, Staszewski L, Xu H, Durick K, Zoller M, Adler E. Human receptors for sweet and umami taste. Proc Natl Acad Sci U S A. 2002 Apr 2;99(7):4692-6
• DuBois GE. Molecular mechanism of sweetness sensation. Physiol Behav. 2016 Oct 1;164(Pt B):453-463.
• Yang L, Ciu M, Liu B. Current Progress in Understanding the Structure and Function of Sweet Taste Receptor. J Mol Neurosci. 2021 Feb;71(2):234-244.
• Sukumaran SK, Palayyan SR. Sweet Taste Signaling: The Core Pathways and Regulatory Mechanisms. Int J Mol Sci. 2022 Jul 26;23(15):8225.
• Mafi A, Kim SK, Chou KC, Güthrie B, Goddard WA 3rd. Predicted Structure of Fully Activated Tas1R3/1R3' Homodimer Bound to G Protein and Natural Sugars: Structural Insights into G Protein 7000Activation by a Class C Sweet Taste Homodimer with Natural Sugars. J Am Chem Soc. 2021 Oct 13;143(40):16824-16838.

Sweeteners & Sweetness

• Belloir C, Neiers F, Briand L. Sweeteners and sweetness enhancers. Curr Opin Clin Nutr Metab Care. 2017 Jul;20(4):279-285.
• Ҫiçek SS. Structure-Dependent Activity of Plant-Derived Sweeteners. Molecules. 2020 Apr 22;25(8):1946.
• DuBois, G.E., “Sweetness and Sweeteners: What Is All the Excitement About?” (2008).
• DuBois GE, Prakash I. Non-caloric sweeteners, sweetness modulators, and sweetener enhancers. Annu Rev Food Sci Technol. 2012;3:353-80.
• Kim, N.C., Kinghorn, A.D. Highly sweet compounds of plant origin. Arch Pharm Res 25, 725–746 (2002).
• Kusakabe, Y, Shindo, Y, Kawai, T, Maeda-Yamamoto, M, Wada, Y. Relationships between the response of the sweet taste receptor, salivation toward sweeteners, and sweetness intensity. Food Sci Nutr. 2021; 9: 719– 727.
• Nabors, L. O., and R. Gelardi. "Alternative sweeteners: an overview. Food science and technology New York-Marcel Dekker- (2001): 1-12.
• Kim, N.C., Kinghorn, A.D. Highly sweet compounds of plant origin. Arch Pharm Res 25, 725–746 (2002).
• Kusakabe, Y, Shindo, Y, Kawai, T, Maeda-Yamamoto, M, Wada, Y. Relationships between the response of the sweet taste receptor, salivation toward sweeteners, and sweetness intensity. Food Sci Nutr. 2021; 9: 719– 727.

Ingestion Impact of Saliva and Mucosa:

• Canon F, Neiers F, Guichard E. Saliva and Flavor Perception: Perspectives. J Agric Food Chem. 2018 Aug 1;66(30):7873-7879.
• Dadmohammadi Y, Torabi H, Davachi SM, Childs M, Cao V, Abbaspourrad A. Physicochemical interactions between mucin and low-calorie sweeteners: Real-time characterization and rheological analyses, LWT, Volume 159, 2022, 113252

Class C GPCR:

• Ellaithy A, Gonzalez-Maeso J, Logothetis DA, Levitz J. Structural and Biophysical Mechanisms of Class C G Protein-Coupled Receptor Function. Trends Biochem Sci. 2020 Dec;45(12):1049-1064.
• Liu H, Li Y, Gao Y. Asymmetric activation of class C GPCRs, Progress in Molecular Biology and Translational Science, Academic Press, 2022

Cell-based assays and receptor expression

• Smith NJ, Grant JN, Moon JI, So SS, Finch AM. Critically evaluating sweet taste receptor expression and signaling through a molecular pharmacology lens. FEBS J. 2021 Apr;288(8):2660-2672.
• Park J, Selvam B, Sanematsu K, Shigemura N, Shukla D, Procko E. Structural architecture of a dimeric class C GPCR based on co-trafficking of sweet taste receptor subunits. J Biol Chem. 2019 Mar 29;294(13):4759-4774.
• Shimizu M, Goto M, Kawai T, Yamashita A, Kusakabe Y. Distinct human and mouse membrane trafficking systems for sweet taste receptors T1r2 and T1r3. PLoS One. 2014 Jul 16;9(7):e100425.
• Belloir C, Brulé M, Tornier L, Neiers F, Briand L. Biophysical and functional characterization of the human TAS1R2 sweet taste receptor overexpressed in a HEK293S inducible cell line. Sci Rep. 2021 Nov 15;11(1):22238.

In vitro culture of human taste cells

• Ozdener MH, Brand JG, Spielman AI, Lischka FW, Teeter JH, Breslin PA, Rawson NE. Characterization of human fungiform papillae cells in culture. Chem Senses. 2011 Sep;36(7):601-12.
• Ozdener MH, Rawson NE. Primary culture of mammalian taste epithelium. Methods Mol Biol. 2013;945:95-107.

Bitter taste receptors and signaling

• Chandrashekar J, Mueller KL, Hoon MA, Adler E, Feng L, Guo W, Zuker CS, Ryba NJ. T2Rs function as bitter taste receptors. Cell. 2000 Mar 17;100(6):703-11.
• Behrens M, Ziegler F. Structure-Function Analyses of Human Bitter Taste Receptors-Where Do We Stand? Molecules. 2020 Sep 26;25(19):4423.
• Kuhn C and Meyerhof W. Oligomerization of Sweet and Bitter Taste Receptors. Chapter 13, Methods in Cell Biology, Volume 117, 2013
• Brockhoff A, Behrens M, Niv MY Meyerhof W. Structural requirements of bitter taste receptor activation PNAS, 11110-111115, 107(24) 2010

Olfaction

• Sharma A, Kumar R, Aier I, Semwal R, Tyagi P, Varadwaj P. Sense of Smell: Structural, Functional, Mechanistic Advancements and Challenges in Human Olfactory Research. Curr Neuropharmacol. 2019;17(9):891-911.
• Kurian SM, Naressi RG, Manoel D, Barwich AS, Malnic B, Saraiva LR. Odor coding in the mammalian olfactory epithelium. Cell Tissue Res. 2021 Jan;383(1):445-456.
• Audouze K, Tromelin A, LeBon AM, Belloir C, Peterson RK, Kristiansen K, Brunak S, Taboureau O. Identification of Odorant-Receptor Interactions by Global Mapping of the Human Odorome. PLoS ONE 9(4): e93037. doi:10.1371/journal.pone.0093037
• Mainland J, Li YR, Zhou T, Liu WLL, Matsunami H. Human Olfactory Receptor Responses to Odorants. Sci. Data 2:150002 doi: 10.1038/sdata.2015.2 (2015)

On March 19, 2024, MIT and The Coca-Cola Company are hosting a virtual networking workshop for the Alternatives to Sugar Grand Challenge.

The Grand Challenge is seeking proposals for interdisciplinary projects that can revolutionize the scientific understanding of sweet taste, that can uncover novel ways for improving sweet taste quality, and that can create game-changing sweetening solutions.

This workshop has two main goals:

1. To help provide information related to the vision, focus areas, and addition information for developing qualifying proposals.
2. To act as a networking event to introduce interest MIT faculty members and researchers from around the world to each other in order to help foster collaborations.

We hope this workshop can bring together research teams to focus on four areas of the challenge: advances in taste and smell science, tools for screening sweetness, innovative chemical approaches to taste, and the use of machine learning and AI in taste research.

To register for the upcoming networking workshop March 19, 2024, please use the following link:

All workshop participants must meet Grand Challenge eligibility requirements. Admission is at the discretion of CBI.