Parasites have clocks Should FCT fund discovery research

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Parasites have clocks Should FCT fund discovery research, or should it follow an agenda

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

Trypanosoma brucei causes sleeping sickness and nagana Trypanosoma brucei Extracellular, unicellular parasite. Transmitted from

Trypanosoma brucei causes sleeping sickness and nagana Trypanosoma brucei 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 Dogma Parasites are essentially the

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

Rotation of earth = predictable time changes Human Circadian rhythms: • Sleep-wake cycle •

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.

Many organisms have internal clocks Do parasites have circadian clocks? May be yes. May

Many organisms have internal clocks Do parasites have circadian clocks? May be yes. May be not. All other organisms have clocks. Parasites probably benefited from clocks during evolution. 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.

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 Digital health Precision medicine & biomarkers Innovative therapies and diagnostics 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.

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

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:

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

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

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

Sensitivity to drugs varies with time of the day Parasites are more resistant to

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

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

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

Discovery research takes us to unexpected destinations Parasites have circadian clocks; Possible chronotherapy ?

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

Core Facilities Histo. Pathology (Tânia Carvalho) Animal House FACS Nuno Collaborators Barbosa-Morais Joseph Takahashi

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