Mart Toots will defend his doctoral thesis titled „Novel Means to Target Human Papillomavirus Infection“ on 5 May 2016 at 9.15.
Supervisors: vanemteadur Ene Ustav (Tartu Ülikool), professor Mart Ustav (Tartu Ülikool)
Opponent: professor Karl Munger, PhD, Tufts University, Sackler School of Graduate Biomedical Sciences, Department of Developmental, Molecular and Chemical Biology, 150 Harrison Avenue, Jaharis 607, Boston MA 02111 USA.
Summary: Most individuals at some point during their life will be infected with Human Papillomaviruses (HPVs). Usually the infection is asymptomatic or results in the formation of benign lesions like warts, which will be cleared by the immune system. However, in rare cases, infection with High-risk HPVs becomes persistent and can eventually cause various carcinomas, most commonly cervical carcinomas. There are more than half a million new cervical carcinoma cases diagnosed every year. HPV infection could be prevented through vaccination but there is no cure against an ongoing infection.
Drug development usually begins by screening chemical libraries containing thousands of compounds, against the target of interest. This kind of screening requires specific assay systems. Most important outcome of this work was the development of such a model system for anti-HPV drug screening. This system uses easily quantifiable reporter genes Renilla and Firefly luciferase to describe the effect of the compound on HPV replication. Using this system five new compounds specifically inhibiting the replication of High-risk HPVs. Analyses of the target proteins of those compounds revealed new pathways which are absolutely necessary for HPV replication; and which could be used as targets when designing new anti-HPV compounds.