Parasites have clocks iMM-Lisboa Should FCT fund discovery research, Luísa Figueiredo Encontro Ciência 2017 Centro de Congressos de Lisboa 5th July 2017 iMM-Lisboa Should FCT fund discovery research, or should it follow an agenda?

Trypanosoma brucei causes sleeping sickness and nagana Extracellular, unicellular parasite. Transmitted from one host to the next by a Tsetse fly. MSF HUMANS. Sleeping sickness is a fatal disease. No vaccine. Treatment is toxic. Active screening has been very effective. ANIMALS. Nagana in cattle is a major contributor to poverty. Economic impact US$4.5 billion in East Africa. WHO report, 2014

The life cycle of Trypanosoma brucei… and its dogmas Parasites are essentially the same regardless of time of the day Dogma

Rotation of earth = predictable time changes Human Circadian rhythms: Sleep-wake cycle Body temperature Hormones Immune defenses Circadian clocks allow humans to anticipate the 24 hr environmental changes.

Do parasites have circadian clocks? Many organisms have internal clocks Do parasites have circadian clocks? May be yes. All other organisms have clocks. Parasites probably benefited from clocks during evolution. May be not. Parasites don’t need clocks. Parasites are not exposed to light - they are always inside a host.

Do parasites have circadian clocks? Discovery research. Also known as basic or fundamental research. Who should fund discovery research? Does this research match the agenda for research and innovation 2030? Healthy ageing Precision medicine & biomarkers Innovative therapies and diagnostics Digital health Evaluation of intervention strategies We regret to inform that your project was not funded…

Do parasites have circadian clocks? Discovery research. Also known as basic or fundamental research. Who should fund discovery research? Does this research match the agenda for research and innovation 2030? “We fund researchers, not projects.”

Do parasites have a circadian clock? Rijo-Ferreira F. et al., Nature Micro 2017

Molecular tools to assess if parasites vary with time Extract RNA of parasites at: 0 hr 4 8 … 40 44 48 hr RNAseq (analysis of BIG DATA)

RNA levels vary with time of the day “Lots” of RNA TRANSCRIPTOME “Little” of RNA

Sensitivity to drugs varies with time of the day Parasites are more resistant to drug Parasites are more sensitive to drug Chronotherapy as a mean to improve treatment efficacy?

Discovery research with potential clinical application Parasites have an internal circadian clock. May be treatment should be administered at a given time of the day (Chronotherapy).

Do parasites have circadian clocks? Who wants/should fund this research? Does this research match the agenda for research and innovation 2030? Healthy ageing Precision medicine & biomarkers Innovative therapies and diagnostics Evaluation of intervention strategies Digital health

Discovery research takes us to unexpected destinations Parasites have circadian clocks; Possible chronotherapy ? ? Who should fund the jeeps?

Core Facilities Collaborators Nuno Barbosa-Morais iMM Lisboa HistoPathology (Tânia Carvalho) Animal House FACS Collaborators Joseph Takahashi (UTSouthwester, Dallas, USA) Nuno Barbosa-Morais (iMM Lisboa) Terry Smith (St. Andrews University, Scotland) Frederic Bringaud (U. Bordeaux, France) Falk Butter (U. Mainz, Germany) Liam Morrison (Roslin Institute, Edinburgh, Scotland) Nuno Barbosa-Morais iMM Lisboa