MILESTONE
Update due 12/15/2018
Gantt Chart (downloadable version)
UCI Malaria Initiative | Decision point | ||||||||||||
| PI: | James | Milestone | Project Start date | 4/1/17 | 4/1/18 | ||||||||
| Specific Aim | Activity | Milestone or Decision Point | Group | Year | 1 | Year | 2 | ||||||
6/30/17 | 9/30/17 | 12/15/17 | 3/30/18 | 6/30/18 | 9/30/18 | 12/15/18 | 3/30/19 | ||||||
Objective 1: Project Administration | |||||||||||||
| 1. Recruit Project Personnel | 1. Write Job Description/announcements | 1.1.1 | UCI | 1.1.1a | |||||||||
| 2. Advertise positions | 1.1.2 | UCI | 1.1.2a | ||||||||||
| 3. Interview Candidates | 1.1.3 | UCI | 1.1.3a | ||||||||||
| 4. Fill positions | 1.1.4 | UCI | 1.1.4a | ||||||||||
| 2. Develop comprehensive Project Plan | 1. Develop draft project plan | 1.2.1 | UCI | 1.2.1a | |||||||||
| 3. Develop decision-making protocol | 1. Develop decision making protocol | 1.3.1 | UCI | 1.3.1a | |||||||||
| 4. Develop commications strategy | 1. Reactive plan | 1.4.1 | All | 1.4.1a | |||||||||
| 2. Proactive plan | All | 1.4.2a | |||||||||||
| 5. Develop central web portal | 1. Develop central website | 1.5.1 | UCI | 1.5.1a | 1.5.1b | ||||||||
| 2. Update website | 1.5.2 | UCI | 1.5.2a | 1.5.2b | 1.5.2c | ||||||||
| 6. Develop regulatory plan | 1. Implement procedures for tracking research-related regulatory requirements (IBC, IACUC, CDC, USDA, others) | 1.6.1 | All | 1.6.1a | 1.6.1b | 1.6.1c | 1.6.1d | ||||||
| 2.Review and develop knowledge base for regulatory requirements for potential field sites | 1.6.2 | UCI, UCD | 1.6.2a | 1.6.2b | 1.6.2c | 1.6.2d | |||||||
| 3. Work with field team to obtain necessary permits | 1,6.3 | UCI, UCD | 1.6.3a | 1.6.3b | 1.6.3c | 1.6.3d | |||||||
| 7. Annual meeting of project participants | 1. Host annual meeting | 1.7.1 | UCI | 1.7.1a | 1.7.1b | ||||||||
Objective 2: Develop and test Anopheles gambiae strains carrying autonomous gene-drive systems linked to anti-pathogen effector genes. | |||||||||||||
| 1. Recruit Project Personnel | 1. Write Job Description/announcements | 2.1.1 | UCI, UCSD | 2.1.1a | |||||||||
| 2. Advertise positions | 2.1.2 | UCI, UCSD | 2.1.2a | ||||||||||
| 3. Interview Candidates | 2.1.3 | UCI, UCSD | 2.1.3a | ||||||||||
| 4. Fill positions | 2.1.4 | UCI, UCSD | 2.1.4a | ||||||||||
| 2. Develop CRISPR/Cas9 gene-drive systems for Anopheles gambiae | 1. Identify and clone appropriate promoter sequences (for example, β2-tubulin, U6, vitellogenin, carboxypeptidase, G12) for expressing CRISPR/Cas9 gene-drive system components | 2.2.1 | UCI, UCSD | 2.2.1a | |||||||||
| 2. Identify An. gambiae fitness-neutral mosquito chromosomal loci, chromosomal loci conferring decreased mosquito fitness, and chromosomal loci that affect parasite propagation in the vector | 2.2.2 | UCI, UCSD | 2.2.2a | ||||||||||
| 3. Design and synthesize gene-drive constructs, and verify sequence | 2.2.3 | UCI, UCSD | 2.2.3a | 2.2.3b | 2.2.3c | ||||||||
| 3. Engineer additional anti-parasite effector genes | 1. Develop additional single-chain (scFv) immunological reagents to inactivate P. falciparum (Pfs47 with Barrillas-Mury, NIH; Pfs230 with Narum, NIH; Ashley Birkett, PATH) | 2.3.1 | UCI, UCSD | 2.3.1a | 2.3.1b | 2.3.1c | |||||||
| 2. Develop alternative effector molecules based on engineered synthetic receptors (SM1) | 2.3.2 | UCI, UCSD | 2.3.2a | 2.3.2b | 2.3.2c | ||||||||
| 3. Make An. gambiae transgenic lines to test additional effector genes using transposon-mediated transgenesis | 2.3.3 | UCI, UCSD | 2.3.3a | 2.3.3b | 2.3.3c | ||||||||
| 4. Perform challenge assays with P. falciparum to determine efficacy of novel effector constructs | 2.3.4 | UCI, UCSD | 2.3.4a | 2.3.4b | 2.3.4c | ||||||||
| 4. Generate transgenic mosquitoes carrying gene-drive elements and the parasite-resistance genes | 1. Perform microinjection experiments, screen resulting insects, and validate integrated DNA to generate gene-drive lines with linked anti-parasite effector genes | 2.4.1 | UCI, UCSD | 2.4.1a | 2.4.1b | 2.4.1c | |||||||
| 5. Develop and maintain detailed laboratory standard operating procedures (SOPs) | 1. Develop and maintain detailed laboratory standard operating procedures (SOPs) | 2.5.1 | UCI, UCSD | 2.5.1a | 2.5.1b | 2.5.1c | |||||||
| 6. Test the performance characteristics of the strains (drive- and parasite-challenge assays) | 1. Conduct parasite challenge assays on transgenic An. gambiae lines | 2.6.1 | UCI, UCSD | 2.6.1a | 2.6.1b | 2.6.1c | |||||||
| 2. Conduct in-depth mathematical modeling studies regarding the predicted behavior of gene-drive systems in different environmental scenarios and then test these predictions in the laboratory | 2.6.2 | UCB, UCI, UCSD | 2.6.2a | 2.6.2b | 2.6.2.c | ||||||||
| 3. Final recommendation for release strain(s) | 2.6.3 | All | 2.7.1a | ||||||||||
Objective 3: Evaluate field site(s) for population alteration trials | |||||||||||||
| 1. Recruit Project Personnel | 1. Write Job Description/announcements | 3.1.1 | UCD, UCB, UCLA | 3.1.1a | |||||||||
| 2. Advertise positions | 3.1.2 | UCD | 3.1.2a | ||||||||||
| 3. Interview Candidates | 3.1.3 | UCD | 3.1.3a | ||||||||||
| 4. Fill positions. | 3.1.4 | UCD | 3.1.4a | ||||||||||
| 2. Evaluation of Potential Field Sites for Selection of Four Candidate Sites | 1. Literature survey for the evaluation of 13 potential GEM field trial sites | 3.2.1 | UCD | 3.2.1a | |||||||||
| 2. Analysis of remotely sensing data for 13 potential field sites. | 3.2.2 | UCD, UCLA | 3.2.2a | ||||||||||
| 3. Select, based on set criteria, four candidate sites. | 3.2.3 | UCD, UCB, UCLA | 3.2.3a | ||||||||||
| 3. Evaluation of Candidate Field Sites for Selecting Final Field Trial Site | 1. Prepare site visits to four candidate field sites and nearest mainland. | 3.3.1 | UCD, UCB, UCLA | 3.3.1a | 3.3.1b | 3.3.1c | |||||||
| 2. Visit villages on each candidate site and nearest mainland to collect Anopheles specimens. | 3.3.2 | UCD | 3.3.2a | 3.3.2b | 3.3.2c | 3.3.2d | |||||||
| 3. Analysis of genotype data to assess entomological parameters | 3.3.4 | UCD | 3.3.4a | 3.3.4b | 3.3.4c | ||||||||
| 4. Analysis of insecticide resistance | 3.3.5 | UCD | 3.3.5a | 3.3.5b | 3.3.5c | ||||||||
| 6. Analysis of genome data to assess degree of genetic isolation of sites | 3.3.6 | UCD | 3.3.6a | 3.3.6b | 3.3.6c | ||||||||
| 7. Model evaluation of candidate field sites | 3.3.7 | UCB | 3.3.7a | 3.3.7b | 3.3.7c | ||||||||
| 4. Assess “Colonizability” of An. gambiae from Candidate Field Sites | 1. Establish mosquito rearing protocols & insectary at UC Davis | 3.4.1 | UCD | 3.4.1a | 3.4.1b | 3.4.1c | |||||||
| 2. Assess ease of colonization for An. gambiae for each site | 3.4.2 | UCD | 3.4.2a | 3.4.2b | 3.4.2c | ||||||||
| 5. Select Field Trial Site | 1. Prepare a written evaluation of each of the four candidate sites. | 3.5.1 | UCD, UCB, UCLA | 3.5.1a | |||||||||
| 2. Make final decision on the project field site(s) | 3.5.2 | All | 3.5.2a | ||||||||||
| Legend: | UCB: University of California - Berkeley | UCLA: University of California - Los Angeles | |||||||||||
| UCD: University of California, Davis | UCSD: University of California - San Diego | ||||||||||||
| UCI: University of California, Irvine | |||||||||||||