Functional Genetics of Infectious Diseases Unit
Institut Pasteur 25-28 rue du docteur Roux, 75015 Paris
Research area of the Unit
Our unit studies the basis of human genetic susceptibility to major mosquito-borne infections, malaria and dengue. We aim not only to identify new genes governing different infection outcomes, such as disease presentation and transmissibility, but also to understand how the different alleles of these genes affect the trait. Identifying key factors underlying an outcome of interest becomes increasingly problematic as the number of variables increases and they do not work independently. We are working on creating a mathematical platform to exhaustively explore retrospective and prospective biological and epidemiological data sets and to generate hypotheses that will provide the framework for the development of predictive models of disease risk. We will learn from experimental datasets of biomolecular interactions from a cellular functional genomics model. This model allows us to integrate interactome data with genome wide genetic study.
Contribution to the programme
The group will contribute to the human genetics part of the programme. There is increasing evidence that pathogens adhere to predictions derived from evolutionary theory, thereby enabling identification of factors for targeting in the development of public health intervention strategies. Thus, a better understanding of the epidemiology of pathogens can be gained through an appreciation of adaptations that govern pathogen transmission from man, or the vertebrate host for anthropozoonotic diseases, to the invertebrate vector. Hence, we can combat certain pathogens, even those that are endemic, by eliminating the source of infection. This is particularly true for emerging diseases. It is therefore necessary to identify, in the infectious disease reservoir, those individuals responsible for transmission (often asymptomatic), and according to the pathogen in question, establish the role played by man.
They have established strong collaboration with several countries including Thailand, Cambodia, Laos, Vietnam, India, Senegal, Madagascar, French Guiana, Brazil, Argentina, Peru and Cuba.
References over the past 5 years
1.      Dussart P, Baril L, Petit L, Beniguel L, Quang LC, Ly S, Azevedo Rdo S, Meynard JB, Vong S, Chartier L, Diop A, Sivuth O, Duong V, Thang CM, Jacobs M, Sakuntabhai A, Nunes MR, Huong VT, Buchy P, Vasconcelos PF. Clinical and Virological Study of Dengue Cases and the Members of Their Households: The Multinational DENFRAME Project. PLoS Negl Trop Dis. 2012 Jan;6(1):e1482.
2.      Loucoubar C, Goncalves B, Tall A, Sokhna C, Trape JF, Diène Sarr F, Faye J, Badiane A, Ly AB, Diop A, Bar-Hen A, Bureau JF, Sakuntabhai A, Paul R. Impact of changing drug treatment and malaria endemicity on the heritability of malaria phenotypes in a longitudinal family-based cohort study. PLoS One. 2011;6(11):e26364. Epub 2011 Nov 3.
3.      Khor CC, Chau TN, Pang J, Davila S, Long HT, Ong RT, Dunstan SJ, Wills B, Farrar J, Van Tram T, Gan TT, Binh NT, Tri le T, Lien le B, Tuan NM, Tham NT, Lanh MN, Nguyet NM, Hieu NT, Van N Vinh Chau N, Thuy TT, Tan DE, Sakuntabhai A, Teo YY, Hibberd ML, Simmons CP. Genome-wide association study identifies susceptibility loci for dengue shock syndrome at MICB and PLCE1. Nat Genet. 2011 Oct 16;43(11):1139-41. doi: 10.1038/ng.960.
4.      Loucoubar C, Paul R, Bar-Hen A, Huret A, Tall A, Sokhna C, Trape JF, Ly AB, Faye J, Badiane A, Diakhaby G, Sarr FD, Diop A, Sakuntabhai A, Bureau JF. An exhaustive, non-euclidean, non-parametric data mining tool for unraveling the complexity of biological systems - novel insights into malaria. PLoS One. 2011;6(9):e24085. Epub 2011 Sep 9.
5.      Lawaly YR, Sakuntabhai A, Marrama L, Konate L, Phimpraphi W, Sokhna C, Tall A, Sarr FD, Peerapittayamongkol C, Louicharoen C, Schneider BS, Levescot A, Talman A, Casademont I, Menard D, Trape JF, Rogier C, Kaewkunwal J, Sura T, Nuchprayoon I, Ariey F, Baril L, Singhasivanon P, Mercereau-Puijalon O, Paul R. Heritability of the human infectious reservoir of malaria parasites. PLoS One. 2010 Jun 29;5(6):e11358.
6.      Louicharoen C, Patin E, Paul R, Nuchprayoon I, Witoonpanich B, Peerapittayamongkol C, Casademont I, Sura T, Laird NM, Singhasivanon P, Quintana-Murci L, Sakuntabhai A. Positively selected G6PD-Mahidol mutation reduces Plasmodium vivax density in Southeast Asians. Science. 2009 Dec 11;326(5959):1546-9.
7.      Jallow M, Teo YY, Small KS, Rockett KA, Deloukas P, Clark TG, Kivinen K, Bojang KA, Conway DJ, Pinder M, Sirugo G, Sisay-Joof F, Usen S, Auburn S, Bumpstead SJ, Campino S, Coffey A, Dunham A, Fry AE, Green A, Gwilliam R, Hunt SE, Inouye M, Jeffreys AE, Mendy A, Palotie A, Potter S, Ragoussis J, Rogers J, Rowlands K, Somaskantharajah E, Whittaker P, Widden C, Donnelly P, Howie B, Marchini J, Morris A, Sanjoaquin M, Achidi EA, Agbenyega T, Allen A, Amodu O, Corran P, Djimde A, Dolo A, Doumbo OK, Drakeley C, Dunstan S, Evans J, Farrar J, Fernando D, Hien TT, Horstmann RD, Ibrahim M, Karunaweera N, Kokwaro G, Koram KA, Lemnge M, Makani J, Marsh K, Michon P, Modiano D, Molyneux ME, Mueller I, Parker M, Peshu N, Plowe CV, Puijalon O, Reeder J, Reyburn H, Riley EM, Sakuntabhai A, Singhasivanon P, Sirima S, Tall A, Taylor TE, Thera M, Troye-Blomberg M, Williams TN, Wilson M, Kwiatkowski DP; Wellcome Trust Case Control Consortium; Malaria Genomic Epidemiology Network. Genome-wide and fine-resolution association analysis of malaria in West Africa. Nat Genet. 2009 May 24.