Studies on Understanding Individual Willingness to Disclose Genetic Information to Public and Private Stakeholders

While technologies for genetic sequencing have increased the promise of personalized medicine, they simultaneously pose threats to personal privacy. The public’s desire to protect itself from unauthorized access to information may limit the uses of this valuable resource. To date, there is limited understanding about the public’s attitudes toward the regulation and sharing of such information. We sought to understand the drivers of individuals’ decisions to disclose genetic information to a third party in a setting where disclosure potentially creates both private and social benefits, but also carries the risk of potential misuse of private information. We conducted two separate but related studies. First, we administered surveys to college students and parents, to determine individual attitudes toward and inter-generational influences on the disclosure decision. Second, we conducted a game-theory based experiment that assessed how participants’ decisions to disclose genetic information are influenced by societal and health factors. Key survey findings indicate that concerns about genetic information privacy negatively impact the likelihood of disclosure while the perceived benefits of disclosure and trust in the institution receiving the information have a positive influence. The experiment results also show that the risk of discrimination negatively affects the likelihood of disclosure, while the positive impact that disclosure has on the probability of finding a cure and the presence of a monetary incentive to disclose, increase the likelihood. We also study the determinants of individuals’ decision to be informed of findings about their health, and how information about health status is used for financial decisions.

Genetic manipulation of Anopheles stephensi immunity to increase plasmodium falciparum salivary gland sporozoite infection levels

Human malaria is responsible for over 700,000 deaths a year. To stay abreast of the threat posed by the parasite, a constant stream of new drugs and vector control methods are required. This study focuses on a vaccine that has the potential to protect against parasite infection, but has been hindered by developmental challenges. In malaria prevention, live, attenuated, aseptic, Plasmodium falciparum sporozoites (PfSPZ) can be administered as a highly protective vaccine. PfSPZ are produced using adult female Anopheles stephensi mosquitoes as bioreactors. Production volume and cost of a PfSPZ vaccine for malaria are expected to be directly correlated with Plasmodium falciparum infection intensity in the salivary glands. The sporogonic development of Plasmodium falciparum in A. stephensi to fully infected salivary gland stage sporozoites is dictated by the activities of several known components of the mosquito’s innate immune system. Here I report on the use of genetic technologies that have been rarely, if ever, used in Anopheles stephensi Sda500 to increase the yield of sporozoites per mosquito and enhance vaccine production. By combining the Gal4/UAS bipartite system with in vivo expression of shRNA gene silencing, activity of the IMD signaling pathway downstream effector LRIM1, an antagonist to Plasmodium development, was reduced in the midgut, fat body, and salivary glands of A. stephensi. In infection studies using P. berghei and P. falciparum these transgenic mosquitoes consistently produced significantly more salivary gland stage sporozoites than wildtype controls, with increases in P. falciparum ranging from 2.5 to 10 fold. Using Plasmodium infection assays and qRT-PCR, two novel findings were identified. First, it was shown that 14 days post Plasmodium infection, transcript abundance of the IMD immune effector genes LRIM1, TEP1 and APL1c are elevated, in the salivary glands of A. stephensi, suggesting the salivary glands may play a role in post midgut defense against the parasite. Second, a non-pathogenic IMD signaling pathway response was observed which could suggest an alternative pathway for IMD activation. The information gained from these studies has significantly increased our knowledge of Plasmodium defense in A. stephensi and moreover could significantly improve vaccine production.