UC Davis

Work in Progress	Deadline 1	Action this week	Risk/Mitigation Plan	Dependencies	Targets	Original Target date	New date
		Advertise positions			3.1.1a	3/30/17	4/30/17
		Advertise positions			3.1.2a	3/30/17	4/30/17
		Interview Candidates	Work covered by existing members		3.1.3a	3/30/17	10/30/17
		Fill positions.	Work covered by existing members	All offers are made and acceptance received as of 11/15/2017. Some will start late.	3.1.4a	9/30/17	2/15/18
		Literature survey for the evaluation of 13 potential GEM field trial sites	Partial list for candidate site was made for July, 2017 field trip	This report will be part of the written report due 12/15/17	3.2.1a	6/30/17	9/30/17
		Analysis of remotely sensing data for 13 potential field sites.		Completed as part of the literature Survey on 13 potential field sites on 9/30/17.	3.2.2a	6/30/17	9/30/17
		Select, based on set criteria, four candidate sites.		Four candidate sites were chosen for visit (Sao Tome, Principe, Annabon, and Comoros) on 12/4/17	3.2.3a	6/30/17	12/5/17
		Prepare site visits to four candidate field sites and nearest mainland.		Site visit to Sao Tome and Principe are scheduled by Anton. Already have valid CDC permit to import samples.	3.3.1a	9/30/17	4/30/17
		Visit villages on each candidate site and nearest mainland to collect Anopheles specimens.		Site visits to Sao Tome and Principe were conducted in May-Jun, 2017	3.3.2a	12/15/17	6/15/17
		Analysis of genotype data to assess entomological parameters		Divergence Island SNP (DIS) assay on Sao Tome and Principe completed on 12/5/2017 (all An. coluzzii and 0 An. gambiae)	3.3.3a	3/30/18	12/15/17
		Analysis of insecticide resistance		DIS assay on Sao Tome and Principe reveals 9% resistant allele in 2017 collections as opposed to 0% in 1998-2003 populations	3.3.4a	3/30/18	12/15/17
		Analysis of genome data to assess degree of genetic isolation of sites	Waiting to hear back additional genetic data (microsatellite genotyping) which include temporal change from our collaborator, Joao Pinto	Linkage disequilibrium between DIS and insecticide resistance alleles support that current resistant Anopheles coluzzii in Sao Tome and Principe may originated from other unknown locations.	3.3.6a	12/15/17	3/30/18
Model evaluation of candidate field sites				Send genetic data to John for his modeling work.	3.3.7a	12/15/17	3/30/18

		Prepare site visits to four candidate field sites and nearest mainland.		Trip scheduled for 3/1/17-3/16/17 field trip in Grand Comore. CDC permit obtained 12/5/2017	3.3.1b	3/30/18	1/30/18
Site visits to Grand Comore and Madagascar			October visit to Madagascar was cancelled due to plague outbreak. Greg will schedule visit in Feb or April.		3.3.2b

UC Berkeley

▪Aim 2.6.2a - In progress

−Aim 2.6.2a - 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

▪Our lab have been developing a mathematical modeling framework, MGDrivE (Mosquito Gene Drive Explorer), specifically to explore the behavior of gene drive systems in realistic landscapes. We have just finished developing an R package to implement this modeling framework. It includes three modules:

−An inheritance module, which incorporates the inheritance dynamics of the gene drive system.

−An ecology module, which incorporates the life cycle of the mosquito vector.

−A landscape module, which incorporates populations of mosquitoes distributed in space and connected via migration.

▪We have begun to explore the spread of threshold-dependent systems through these landscapes.

Ecology module of MGDrivE:

●Mosquitoes progress from eggs to larvae to pupae to male/female adults.

●Genotypes are tracked across life stages and adult females acquire a composite mated genotype based on the male whom they mate with.

●Egg genotypes are distributed according to the inheritance pattern of the gene being considered.

●Density dependence occurs at the larval stage, with larval mortality being a function of the total larval population size.

▪Aim 3.3.7a - In progress

−Aim 3.3.7a - Model evaluation of candidate field sites

▪We have studied the characteristics of the candidate field sites in terms of their suitability for conducting a confined field trial. We concluded that the presence of two sets of two mosquito/human populations, each separated from each other such that only limited mosquito movement occurs between each, would be ideal. This would allow spread and confinement of transgenes to be assessed and repeated.

▪The Comoros Islands are one of the most promising candidate field sites. We have therefore begun to develop landscape modules specifically for these islands, incorporating known human populations around which mosquito populations would be expected, and with mosquito movement incorporated between these populations.

▪Given the importance of mosquito movement for these models, we have begun to develop a pipeline of analysis through which geocoded mosquito genome sequences can be used to inform rates of movement between populations. These methods are based on conservation of long sequence blocks of conserved SNPs.

Goals

▪Use the MGDrivE modeling framework to predict the spread of a variety of homing and remediation systems through structured populations.

▪Rigorously explore homing-based gene drive architectures that display threshold properties and could enable conduct of confined field trials.

▪Fit models to laboratory drive data, when available.

▪Develop landscape modules of MGDrivE for Sao Tome, Principe and Annabon (in addition to Grand Comore).

▪Visit field sites and consider additional details and local data sources that could be helpful in informing these models.

▪Continue to develop the analysis pipeline for inferring mosquito movement rates from geolocated mosquito population genomic data.

Team Updates and Status (Please update Monthly)

UC Davis

UC Berkeley