Team:Evry/Seminar

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Iron coli project


Seminar on hemochromatosis the 18th of September

On the 18th of September, Evry iGEM team organized a seminar on hemochromatosis on iron related diseases. The aim of this seminar is to present the latest scientific advances on thoses diseases and futur treatments. We also take this opportunity to present synthetic biology and our project in iGEM competition to both scientists and patients.

Day's agenda

Start time Speaker Subject
10:00 Gabriel Guillocheau Opening speech
10:15 PHD-DR Gaël Nicolas Iron homeostasis in mammals and its deregulation
11:00 PU-PH Pierre Brissot Hemochromatosis: its diagnostic and its treatment
11:45 Break
12:00 PHD-DR Marie-Paule Roth Link between HFE, hepcidin and BMP6
12:45 Lunch
14:15 Result questionnaire with patients participation
15::00 PHD Nicolas Pollet Microbiom studies
15:45 Break
16:00 iGEM EVRY team A bacterial treatment for hemochromatosis
16:45 Gabriel Guillocheau Closing speech

Report of the day

Gaël Nicolas: "Iron homeostasis in mammals and its deregulation"

Gaël Nicolas

Summary

Iron is necessary to living beings but potentially toxic, that is why homeostasis is required. In a human body there are 4 g to 5 g of iron, that is about a rusted nail. Iron is present as Fe2+ and Fe3+; as Fe3+ it is insoluble and thus must be degraded in Fe2+, but as Fe2+ it becomes highly toxic because it is a strong oxidant. Much of iron is located in the red blood cells. This explains why we associate iron with oxygen transport, but many other reactions imply iron.
In the 1930's, an experiment showed that iron was not excreted by the body: iron remains stocked in the body. We absorb 1 mg to 2 mg of iron daily in order to compensate 1 mg to 2 mg of iron lost daily through the death of cells. The production of red blood cells uses 20 mg of iron daily, but these 20 mg exclusively come from the recycling process of old red blood cells by macrophages.
Hepcidin is a hormone that makes the level of iron in the serum decrease. Hepcidin is thus to iron approximatively what insulin is to glucose. Its deficiency is implied in almost all the forms of hemochromatosis. This hormone has three sulphur bridges, that makes it very difficult to synthesise.

Question/Answer

Q1: What are the consequences of iron overload on red blood cells? Are they not biconcave anymore?
A1: No, they remain biconcave because this feature has been naturally selected and it is necessary for the red blood cells to go through the capillaries. But there may be more of them, or they may be bigger.
Q2: Given the number of persons who have this disease, how is it still possible that doctors do not know it, or can not diagnose it properly?
How can you explain the different forms of the disease (particularly regarding the seriousness) between siblings?

A2: Other genes have effects on iron regulation, so they can increase or decrease the seriousness of the disease. Food have consequences too, and for example the red wine contains much iron. Moreover alcohol reduces the production of hepcidin.
You mentioned doctors. I want to put things in perspective: in France there are around 200 000 doctors, and there are around 200 000 patients, thus a doctor will have on average one case in all his/her career.
Q3: According to you, will the synthetic mini-hepcidin induce an immune response?
A3: The mini-hepcidin is produced with major modifications, so yes.
Q4: Once iron is stored in organs, how can it be eliminated?
A4: It can not, unless by bloodletting.

Pierre Brissot: "Hemochromatosis: its diagnostic and its treatment"

Pierre Brissot

Summary

Hemochromatosis is a frequent genetical disease: in France one person over 300 is predisposed develop it. Indeed, it is a disease with an incomplete penetrance, what means that all the people who are homozygote will not develop the disease. Hemochromatosis is also a delayed disease because the symptoms are long to appear: hemochromatosis is long silent.
The first symptoms are chronic tiredness and rheumatism. As they are not very specific symptoms, 5 to 10 years often pass between their appearance and the diagnosis. The excess deposition of iron has serious consequences on the organs, and first of all on the liver. The liver is indeed the first barrier of the body against iron. The excess deposition of iron in the liver leads to its cirrhosis, and when the liver can stock no more iron, iron goes to the pancreas and the hearth.
The most usual genetic mutation causing hemochromatosis is a mutation of the “iron gene” on the chromosome 6, called C282Y homozygosity. This mutation drastically decrease the production of hepcidin. The genetic test should be done only after a blood test determining iron level. It is also possible to use MRI to see if the liver stocks iron.
Bloodletting forces the organism to use the iron stocks to renew the red blood cells. Bloodletting gives really good results, almost without any side effect, but it is not perfect: for example rheumatism remains. Moreover some patients can not get used to the bloodletting. Iron chelators (in oral treatment) can thus be an alternative to bloodletting, or at least complete bloodletting.

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Marie-Paule Roth: "Link between HFE, hepcidin and BMP6"

Roth

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Result questionnaire with patients participation

GabOtis

Summary

We learned three important informations with our survey.
Most patients are satisfied with bloodletting, and the more satisfied they are, the less they want another treatment. Despite this, they remain interested in a complementary treatment.
The most interested patients are the patients who would benefit the less from the bacterian treatment. Indeed this treatment would be most appropriate after the first phase of treatment, to help regulating iron absorption and diminishing the frequence of bloodletting.
Last but not least, our survey shows that a bacterian treatment would be a real help for working patients, who often have difficulties to leave their job to go to bloodletting.

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Nicolas Pollet: "Microbiom studies"

Nico

Summary

All the micro-organisms that live in (and on) the human body constitute our microbiome. There are 10 times more of them than our own cells, and the microbiome as an all has 1000 times more genes than us. The microbiome is a necessary part of our organism, so there is a large number of beneficial bacterias.
The microbiome is still relatively unknown. We know that it is very complex. The number of micro-organisms increases exponentially along the digestive system; the microbiome varies depending on the place of the body, but also depending on the topology. Our microbiome changes during our live too: for example during pregnancy. Last but not least, we all have different microbiome, but it seems that there are several bacterial patterns. As the microbiome play a role in some pathologies, these patterns may be a major research field, notably in probiotic field.

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iGEM EVRY team: "A bacterial treatment for hemochromatosis"

BBG

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Ressenti de quelques intervenants