Posted By: National Institutes of Health
Category: Scientific/Engineering Skill: Scientific Interest: Science & Research Submission Dates: 2 p.m. ET, Sep 04, 2018 - 2 p.m. ET, Mar 02, 2020
The National Eye Institute (NEI), part of the National Institutes of Health, is seeking in vitro, stem-cell derived 3-D human retina organoids. The goal of the challenge is to generate concrete prototypes of 3-D systems that model the cellular organization and function of the human retina.
Solvers will have 2 opportunities to submit solutions and win prizes.
- Phase 1 deadline: October 1, 2018 at 2:00 pm ET
- Phase 2 deadline: March 2, 2020 at 2:00 pm ET
Evaluation criteria are the same for both phases; at each deadline, teams can submit a solution that includes data supporting the scientific evaluation criteria they have accomplished to date. Full description, rules, and details of this prize competition are defined on NEI’s challenge details page.
NEI is seeking innovative solutions that achieve significant advances over currently available retina organoids. Solutions must show publication-quality data demonstrating:
- A 3-D human retina organoid system that mimics the physiological and morphological features of the in vivo biology, consists of the major retina cell types (rod and cone photoreceptors, horizontal, bipolar, amacrine, and ganglion cells and Muller glia) with appropriate lamination and synaptic organization, and represents their biological functions and interplay. Components (neurons, retinal pigment epithelium [RPE], glia) may be produced separately or dissociated and recombined (1) if protocol is driven by a valuable biological question and (2) if in the process of re-assembly, specific functions/roles of cell types are delineated. Three-dimensional assembly may be achieved using various approaches, for example through self-organization that recapitulates natural development (“true organoid”) or through bioengineering with scaffolds, bioprinting, and/or microfluidic apparatuses.
- Retina organoids that are generated entirely from human cells (e.g. derived from iPSCs, hESCs, multipotent cells, or adult cells subjected to a combination of transdifferentiation/reprogramming methods).
- Modeling and treating retinal disease, or testing and developing drug (i.e., high content screening) therapies.
- Find detailed evaluation criteria here under “Evaluation and Winner Selection”
Explants are not of interest for this Challenge. Tissue-on-a-chip systems that use cells grown in 2-D co-culture and do not fully represent the structure, morphology, and function of the human retina are also not of interest. However, creative approaches that incorporate use of microfluidics or perfusion to enhance culture or extend duration of survival for 3-D organoid systems are acceptable.
Reviewers will be asked to use the following criteria when evaluating whether (in the form of results, graphs, images, etc.) a prototype 3-D human retina organoid meets evaluation criteria:
- Significant advances over currently available protocols in areas such as duration of culture, yield, and maturity/differentiation of all cell types in appropriate numbers and ratio.
- Potential impact on understanding the biology of the retina.
Evaluation Criterion 1. Impact and Innovation (20 points) - 20%
Solutions will be evaluated for creativity and originality of designs. An innovative approach may be novel, groundbreaking, or paradigm-shifting, or a creative application of existing approaches. For Phase 1 submissions, the approach should also be feasible; i.e., have a high likelihood to succeed in meeting or exceeding the scientific evaluation criteria NEI has defined. Overall, the solution should provide a novel solution to building a 3-D human retina that meets the desired scientific criteria (structure, function, morphology). Reviewers will be asked to specifically address:
Impact on potential end users, clinical implications, and therapeutic advances —To what extent will the solution exert a sustained, powerful influence on the understanding of retinal diseases and accelerating research toward new therapies?
To what extent does the solution address a significant barrier in the development of human retina organoids that are highly representative of human physiology? Does the approach speed up organoid development and differentiation time, improve yield, or increase production?
How is the solution unique and does it improve upon state of the science for organoid technology?
To what extent are novel concepts, approaches, methodologies, technologies or instrumentation used, or are existing approaches applied in a novel way?
To what extent are cross-discipline techniques integrated to produce a 3-D human retina organoid prototype that addresses the scientific evaluation criteria? (applicable to Phase 1 only)
Will the innovative solution and team executing it allow all scientific criteria to be met within the timeframe of the Challenge? Are any limitations to the approach discussed and addressed? (only applicable to Phase 1)
Evaluation Criterion 2. Cell Types, Structure, and Function (25 points) - 25%
Solutions will be evaluated for establishment of a human PSC-derived in vitro retina model system that resembles the morphology of a healthy-native retina and is viable through formation of photoreceptor outer segments and/or long-term survival of retinal ganglion cells with extension of axonal processes. Reviewers will be asked to address:
Cell Types: How many neuronal (or neuronal derived) cell types are stably co-cultured (rod and cone photoreceptors, bipolar cells, ganglion cells, horizontal cells, and amacrine cells, Muller glia)? Are long-term viable and functional RPE, choroid or non-neuronal cell types (e.g., pericytes, microglia, astrocytes) incorporated? To what extent does the evidence presented show presence of cell types and 3-dimensional structure. If a cell type is lacking, is there justification for why it is not present and not needed for proof of principle (i.e. the disease being modelled lacks the specific cell type)?
Structure: Are organoid prototypes 3-dimensional and properly oriented? To what extent do the synaptic layers recapitulate those of a laminated retina with multiple neuron classes present in numbers and proportions that represent an in vivo setting (as indicated by biomarkers of lineage and differentiation)? How many other retina and retina-relevant tissues, cells, or structures are included?
Functional characterization of cell types: Are all cell types in the organoid (or added to the organoid) functional through the latest viable timepoint as shown by appropriate analyses, including electrophysiology (e.g., light response and recovery for subsequent responses, etc.), retinoid recycling, cell communication, functional connectivity, fluid transport in RPE, etc.?
Evaluation Criterion 3. Reproducibility, Quality Control, and Standardization (25 points) - 25%
Assessment of inter/intra-laboratory utility, transferability, and reproducibility, with conclusive evidence that organoid prototype is based on a reproducible protocol and the protocol produces a relatively standardized product.
Reproducibility: To what extent do the data support reproducibility and standardization (e.g., data showing transferability to other labs and lack of variability from batch to batch) included? To what extent is documentation of standardization or commercialization highlighted (i.e. cGMP protocols or patent applications)? Are the methods (part of the Appendix) sufficiently detailed such that the efforts could be reproduced (e.g., Standard operating protocols)?
Robustness: How do the data support advances in organoid development to decrease differentiation time, improve yield, or increase production?
Have retina organoids been characterized to show they are free of microbial contamination and chromosomal defects (i.e. karyotyping, STR analysis, FISH analysis)?
Are formal documented agreements with industry, or transferability to industry partners (MOUs, licensing, CRADA, in-kind or discounted validation) presented?
Evaluation Criterion 4. Endpoint Assay Specific Goals (30 points for EITHER category) - 30%
BIOLOGY/DISEASE MODELING (note: NEI is agnostic to which disease is chosen, as long as technology is developed to robustly recapitulate the disease):
Does the organoid prototype demonstrate improvement in faithful biological complexity (e.g. macula, multiple cell subtypes present in physiologically similar ratios, etc.)?
Does the model recapitulate some aspect of disease phenotype in one or more assays?
Viability and scalability: If grown at one organoid/well, are 90% of organoids in a plate viable, as shown by random sampling in five wells across a dish? For how long are morphological and functional features maintained? Are methods that increase the production (e.g., many dozens) of organoids and/or allow the distribution of well-characterized organoids presented to enable multiple organoids to be compared in the same experiment?
Is therapeutic intervention to treat the disease modelled with 3-D retina organoids (e.g. via gene editing, small molecules, cell replacement, etc.) demonstrated?
HIGH CONTENT SCREENING:
Are retina organoid prototypes amenable to high content screening, which may include high content imaging, drug validation/toxicology, or functional genomic screening (e.g. does not include materials known to show strong compound adsorption)?
Does the model recapitulate known retina toxicities based on morphological and functional readouts?
Scalability and portability: Are organoids grown at medium throughput (e.g., in a 96-well plate) robust? When grown at one organoid/well, are 90% of wells in a plate viable, as shown by random sampling in five wells across a dish? For how long are morphological and functional features maintained? Are methods to mass-produce (e.g., 100s) organoids such that multiple plates can be compared in the same experiment included?
- Go to NEI’s challenge details page and see “Registration Process for Participants” and “Submission Requirements and Template.”
- Create an account on Challenge.gov, or use an existing account, to submit your solution, including all information required in the application template.
- Use the application template to format your submissions
- Submit your solutions to challenge.gov:
- Phase 1 solutions must be submitted by 2:00 pm Eastern time on October 1, 2018.
- Phase 2 solutions must be submitted by 2:00 pm ET on March 2, 2020
Add to the Discussion
All details related to rules and eligibility are defined on NEI’s challenge details page. Only complete applications will be reviewed.
- Must follow all rules & guidelines listed on NEI’s challenge details page.
- Must be 18 years of age or older
- May participate individually or as part of one or more teams
- Each team’s designated captain must be a U.S. citizen or permanent resident
- Must use NEI’s application template to format submissions
- Must register and submit abstract on Challenge.gov within one week of submission period opening:
- First round opens September 4, 2018
- Second round opens February 14, 2020
- Must submit solutions by deadlines:
- First round solutions due 2:00 PM Eastern time on October 1, 2018
- Second round solutions due 2:00 PM Eastern time on March 2, 2020
To win prizes:
- Must be a US citizen or permanent resident
- Agree to the eligibility rules and requirements listed on NEI’s challenge details page
- Register and submit solutions on Challenge.gov