{"signature": "0xfa8472ac3ec24e59a6b3b82278ca1ab21d7d28df7231336953a5233b1268a6f51eb88ec4aae7bbf537a0c37f3bb927e5ea7da986d6c0725c9ec2ca5c58e8b8db1b", "application": {"round": "0x0c0412ddb846096ea1e37de717921ebf4fef9a39", "answers": [{"type": "email", "hidden": true, "question": "Email Address", "questionId": 0, "encryptedAnswer": {"ciphertext": "Kh64+48xoatDXqfGxT3xogTSuusBfMk2rI5Y/2dG/AQ=", "encryptedSymmetricKey": "e59c8751d37302741e68a3f22b1d1ceee3a10e9f40c8393bad2b3cb2b0a0b9c054dd8819fbd228057063294d6d00f805d399978650485ce91c32cffa8955c32c50d7df5ec02c61bdc2354c9ba229241ce40788eec4707be27d732783e9d63882a852027945d995b22201de45970adc36d3695cc4f7825e0a38b8f7b660d8f217000000000000002032fd914ebb3609621235f593409adf2d550b005af7d3ef326d7041ded89ccef2fa24a0d4644df81795495a1bc5a86e88"}}, {"type": "short-answer", "answer": "VitaDAO \u00b7 Longevity Hackathon \u00b7 Longevity Prize \u00b7 PrivateAI \u00b7 ResearchHub \u00b7 GG20 \u00b7 personal donations", "hidden": false, "question": "Funding Sources", "questionId": 1}, {"type": "number", "answer": "1", "hidden": false, "question": "Team Size", "questionId": 2}, {"type": "short-answer", "answer": "raimbetov", "hidden": true, "question": "Telegram username", "questionId": 3}, {"type": "paragraph", "answer": "24,000", "hidden": true, "question": "Total prior funding for project in USD", "questionId": 4}, {"type": "paragraph", "hidden": true, "question": "Profiles or socials of other main team members publicly associated with project", "questionId": 5}, {"type": "short-answer", "answer": "32", "hidden": true, "question": "How old is the project? (Months)", "questionId": 6}, {"type": "paragraph", "answer": "[**overlake.bio**](https://overlake.bio/) is an end-to-end decentralized framework, currently encompassing four scientific projects that look into underexplored aspects of human aging. \n\n**Problem 1|** Aging has been conceptualized as an increase in intracellular molecular entropy, leading to dysregulation of vital processes, damage accumulation, and consequent deterioration of physiological resilience, resulting in pathology and, ultimately, death. Deleterious alteration of extracellular structural components, i.e., the extracellular matrix, and the damage accumulated therein as a function of time are an emergent hallmark of aging that could have a profound impact on our understanding of the aging process. Presently, there\u2019s a lack of knowledge on how the damage in the extracellular matrix is linked to other, \u201cclassical\u201d, hallmarks of aging, such as genomic instability, epigenetic alterations, the loss of proteostasis, etc.   \n**Solution 1|** [One of my projects](https://overlake.bio/rakhan/Glycation-of-ribosomes-as-a-driver-of-proteostasis-loss-d8971d87778846349d8f4fc29a91a30b) is dedicated to studying how the increased metabolic flux towards generation of a toxic glycolytic byproduct **methylglyoxal**, arising in response to the damaged extracellular matrix, can result in chemical modification of ribosomes, changing protein synthesis accuracy at the level of mRNA decoding \u2013 i.e., how the damaged extracellular matrix, modulating metabolic pathways, can disrupt proteostasis via a novel mechanism: proteins, produced by the faulty ribosomes, contain errors in their amino acid sequences, making them prone to misfold (aberrantly spatially organize), elicit stress responses, and aggregate. This hypothesis won me the [2nd Longevity Prize](https://www.longevityprize.com/prize/hypothesis). I published my initial results as a [preprint](https://dx.doi.org/10.2139/ssrn.4566939) in 2023\\.\n\n**Problem 2|** Prominently, age-related damage to the extracellular matrix can exist as sugar- and sugar metabolite-derived chemical adducts and crosslinks, called **advanced glycation end products** (AGEs). Given the slow turnover rate of extracellular proteins and the irreversible nature of AGEs, this form of insult tends to accumulate in the extracellular milieu, disrupting normal tissue homeostasis and promoting intracellular entropic events through various mechanisms, manifested as the hallmarks of aging.   \n**Solution 2|** Once formed, AGEs aren\u2019t normally susceptible to repair. One hypothetical way of thwarting or reversing the AGEs accumulation is using engineered biologics, e.g., enzymes designed to act upon glycation intermediates or final adducts/crosslinks, restoring the extracellular matrix to a relatively youthful state. Consequently, [another project of mine](https://overlake.bio/rakhan/Advanced-glycation-end-product-AGE-degrading-enzymes-ce317852187b4639b5e5debe42b62290) aims to create new enzymes that would carry out the task of removing the said noxious chemical modifications, achieving normal homeostasis in aged tissues.\n\n**Problem 3|** Besides the stochastic and purely chemical modifications of the extracellular matrix described above, the latter also changes compositionally, displaying a shift in relative abundance of extracellular proteins and glycans to mirror the cellular physiological state. Although there\u2019s an adequate understanding of what proteins are expressed in the norm, few data exist on what happens with the extracellular matrix composition as humans age.  \n**Solution 3|** Each cell type, within the tissue context, expresses a different set of extracellular proteins. I\u2019m working to create [**The Extracellular Matrix Aging Atlas**](https://overlake.bio/rakhan/Extracellular-matrix-aging-atlas-10e0f2ecd2f545afad43fd971cce5be7), a knowledgebase of time-resolved proteomic signatures, derived from published datasets, that would integrate cross-sectional and longitudinal studies scattered across the literature in a comparable and scalable manner. Such a database will serve as a handy tool for looking into compositional dynamics of aging tissues, possibly highlighting common themes across tissues/organs and pinpointing targetable components.\n\n**Problem 4|** Finally, my vision for the longevity research expands and blends into space exploration. I\u2019m convinced that as humanity forays into deep space and attempts to colonize other worlds, it will inevitably face harsh conditions it\u2019s not biologically equipped to withstand: e.g., challenges of microgravity, radiation, unsteady circadian rhythm, isolation.  \n**Solution 4|** My [**Spacefarer Phenome**](https://overlake.bio/rakhan/Spacefarer-phenome-6df641ad372c4ac5a64b8a666d30a179) project is the concept for an optimized collection of human phenotypic traits, dictated by genetics, that are specifically adapted for the rigors of space exploration and life in extraterrestrial environments. It encompasses the idea of identifying or engineering these traits to enhance human resilience against space-related challenges, aiming to improve the feasibility and sustainability of long-duration space missions and off-world colonization.", "hidden": false, "question": "Describe your project in a few paragraphs (ideally including a problem statement, solution, roadmap, and timeline for implementation)", "questionId": 7}, {"type": "paragraph", "answer": "[**overlake.bio**](https://overlake.bio/) is the first (and the only) example of a fully decentralized hard science initiative, funded via web3 mechanisms and independently executed, that published preprints with a DAO as the corresponding author\u2019s sole professional affiliation.\n\nMy next step is to advance two of my preprints as first-ever, end-to-end decentralized, peer-reviewed scientific articles\u2014an experimental paper and a review\u2014establishing DeSci as a valid standalone framework for scientific endeavor. ", "hidden": false, "question": "How does your project support the mission or goals of DeSci?", "questionId": 8}, {"type": "paragraph", "answer": "I\u2019m looking to raise funds in support of publishing two manuscripts in open-access, peer-reviewed journals by the end of the year:\n\n**1|** [**Methylglyoxal affects translation fidelity**](https://dx.doi.org/10.2139/ssrn.4566939). I complemented my initial experimental data with bioinformatics analysis and am aiming to submit the manuscript to [*Biochemical and Biophysical Research Communications*](https://www.sciencedirect.com/journal/biochemical-and-biophysical-research-communications) (BBRC) as a short communication. This will be the first DeSci \u203c\ufe0f**experimental paper** ever published in a traditional scientific outlet.\n\n**2|** [**Strengths and weaknesses of longevity biomarkers**](https://doi.org/10.55277/ResearchHub.dxewpyv0). This is a review paper surveying the biomarker landscape to predict life- and healthspan; it had been conceived on the VitaDAO discussion forum and was executed in a decentralized fashion. In case accepted to [*Frontiers in Aging*](https://www.frontiersin.org/journals/agingc), it\u2019ll be the first DeSci \u203c\ufe0f**review paper** ever published in a scientific journal.\n\nBesides the publishing efforts\u2014in case you liked what I do\u2014please consider donating to help me continue to work on my projects and stay DeSci for as long as possible.", "hidden": false, "question": "Describe how funds from the grants program will be used for your project. ", "questionId": 9}, {"type": "paragraph", "hidden": true, "question": "If you participated in past grant rounds (i.e. DeSci GR15/ Beta) using a different project payout wallet address, please share it here.", "questionId": 10}, {"type": "paragraph", "answer": "I participated with an early version of [**Spacefarer Phenome**](https://explorer.gitcoin.co/\\#/round/42161/39/31) in the **GG20** DeSci round. At the moment, the project is at the ideation/data collection stage without major shareable updates.", "hidden": false, "question": "If this project participated in past grant rounds, please share any new updates or milestones since the last round.", "questionId": 11}, {"type": "paragraph", "answer": "There\u2019s a few years\u2019 lag between the start of a project and its first fruits. Currently, I\u2019m delivering on the oldest projects, which had been started \\~2 years ago, while newer ones are still at various stages of completion. I\u2019m by all means interested in collaborations and valuable input that would help propel my work toward meaningful milestones. In case you\u2019re interested in contributing, please reach out via [email](mailto:r@overlake.bio).", "hidden": true, "question": "Is there any other information you would like to share about your project, previous work, other project affiliations, or potential conflicts of interest? (or anything not covered elsewhere in this application that you feel is relevant to share)", "questionId": 12}, {"type": "checkbox", "answer": ["Yes"], "hidden": false, "question": "Does 50% of your team reflect the diversity of the community your project serves with a particular emphasis on including women, Black, Indigenous, and People of Color (BIPoC), individuals with disabilities, and members of the LGBTQ+ community?", "questionId": 13}, {"type": "multiple-choice", "hidden": true, "question": "Please read the following exclusion criteria that are not permitted and will result in rejection or removal from the round.", "questionId": 14}], "project": {"id": "0xea25111408ed7d55f7beef179290fb8bdf9c1aadf78fa90526ba36a445f42bb6", "title": "overlake.bio", "logoImg": "bafkreih7krpdycgargvkz7zedlvp7kdhif326bqlyqmlturh3yr5ylhpxq", "metaPtr": {"pointer": "bafkreih3xkyy5oi4ocgfzoeskx25fke742kskdyq3tsmfnp2pbzeuu32tm", "protocol": "undefined"}, "website": "https://overlake.bio/", "bannerImg": "bafkreibwbu4euofn5kquxek4xgm7jvbbsrzwerx2vmkaapxjgxlzttymhm", "createdAt": 1723083774646, "credentials": {"twitter": {"type": ["VerifiableCredential"], "proof": {"jws": "eyJhbGciOiJFZERTQSIsImNyaXQiOlsiYjY0Il0sImI2NCI6ZmFsc2V9..7keO3gOiFQeRFtzCkdBBvl1bGm72xGTQ9mhUhbprumsTbMN797fbyM8ohknpnpjXCF6483wIWAGykpJd_YYYBw", "type": "Ed25519Signature2018", "created": "2024-08-08T02:16:20.824Z", "proofPurpose": "assertionMethod", "verificationMethod": "did:key:z6MkghvGHLobLEdj1bgRLhS4LPGJAvbMA1tn2zcRyqmYU5LC#z6MkghvGHLobLEdj1bgRLhS4LPGJAvbMA1tn2zcRyqmYU5LC"}, "issuer": "did:key:z6MkghvGHLobLEdj1bgRLhS4LPGJAvbMA1tn2zcRyqmYU5LC", "@context": ["https://www.w3.org/2018/credentials/v1"], "issuanceDate": "2024-08-08T02:16:20.824Z", "expirationDate": "2024-11-06T02:16:20.824Z", "credentialSubject": {"id": "did:pkh:eip155:1:0x59041d70deAEfe849A48E77e0b273DdD072eA9e4", "hash": "v0.0.0:Q14TlWbmR7/a+dCouG1C64GJ3DWo2N4CN+sjmeHQgPo=", "@context": [{"hash": "https://schema.org/Text", "provider": "https://schema.org/Text"}], "provider": "ClearTextTwitter#overlake_bio"}}}, "description": "[**overlake.bio**](https://overlake.bio/) is an end-to-end DeSci framework comprising a collection of [projects](https://overlake.bio/rakhan/projects-0b1edcacb77e4c93a1b8ad8df47c161d) aimed at promoting human longevity:\n\n**1|** Novel insights into translation fidelity in aging: [**Glycation of ribosomes as a driver of proteostasis loss**](https://overlake.bio/rakhan/Glycation-of-ribosomes-as-a-driver-of-proteostasis-loss-d8971d87778846349d8f4fc29a91a30b)\n\n**2|** Engineered biologics to alleviate the glycation load: [**Advanced glycation end product (AGE)-degrading enzymes**](https://overlake.bio/rakhan/Advanced-glycation-end-product-AGE-degrading-enzymes-ce317852187b4639b5e5debe42b62290)\n\n**3|** A knowledgebase of time-resolved matrisome signatures extracted from public proteomic datasets: [**The Extracellular Matrix Aging Atlas**](https://overlake.bio/rakhan/Extracellular-matrix-aging-atlas-10e0f2ecd2f545afad43fd971cce5be7)\n\n**4|** Customizing human genetics to improve resilience and adaptability for thriving in space exploration and extraterrestrial habitats: [**Spacefarer Phenome**](https://overlake.bio/rakhan/Spacefarer-phenome-6df641ad372c4ac5a64b8a666d30a179)\n\n[**VIDEO**](https://www.loom.com/share/492912664ed1495d97b4c1c33a22b3b4?sid=5fc33f9b-ab8f-4a48-9b5b-df23c1174557) \\[2 min\\]", "lastUpdated": 0, "projectTwitter": "overlake_bio"}, "recipient": "0x59041d70deAEfe849A48E77e0b273DdD072eA9e4"}}