1. 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?

2. 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

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

4. 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.

5. 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.

6. 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…

7. 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.”

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

9. 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)

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

11. 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?

12. 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).

13. 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

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

15. 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