The genomic medicine

A section of DNA; the sequence of the plate-li...

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Hi guys,

check this video out. The general scientific director of National Human Genome Research Institute is showing how to purify DNA from Strawberry by using everyday household items. It is absolutely a fantastic idea that clarifies also the basic chemical principle of the DNA. After all purifying DNA is not so complicate!

Dr. Erik D. Green started his pioneering studies for whole genome analysis during his post-doc at the Washington University School of Medicine genetics department. His complete biography can be found here. Dr. Green has recently published a very interesting review on the achievement of scientific community in the field of genomic with the title: “Charting a course for genomic medicine from base to bedside”. He summarizes 5 principal achievements: understanding the structure of the genome, understanding the biology of the genome, understanding the biology of the disease, advancing the science of medicine and finally improving the effectiveness of health care (by the 2020!). Very interesting review full of very usefull link. Enjoy the reading.

The chimpanzee war

colonisation de l'Europe par Homo sapiens

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Hi Dudes!

So today 12 February 2011 we want to celebrate the 202° birthday of the genius of Darwin. For this Special day our blog participate to the Carnival of Biodiversity, an initiative promoted by Livio Leoni, Marco Ferrari, Lisa Signorile.  Today all the blogs attending this initiative will publish a post dealing about evolution with the title: “Biodiversity and adaptation: the constant competition for food and space”. All the post, including ours, will be listed with a review on the blog Leucophaea (Marco Ferrari) at  this page. So enjoy the reading!

The chimpanzee war

Competition between species, between members of the same species and, as Richard Dawkins would say, between genes, is one of the major “driving forces” of evolution. Individuals developing a new feature (due to random mutation) with competitive advantages for survival and reproduction will pass this information on to the offspring and, as such, a small evolutionary step occurs. The competition can be on different levels: competition for food, for female, for space and in the case of Homo sapiens sapiens also for money and power. In the so called “superior animals” (name refers to their elevated structural complexity) adaptation does not only include physical but also behavioral adaptation. Behavior plays an important role in the game for survival. An example would be fear that pups usually show which protects them from being seen and caught by predators. Furthermore, altruism that parents show for their offspring is important for survival. On the other end of the spectrum there is aggression: within the same species, aggressive behavior may be important when fighting for a female or for food. In this perspective, the history of the Homo sapiens sapiens is full of violence and the more aggressions are organized the more deadly and devastating the final outcome is: holocaust and global war. However, anthropologist Christopher Boehm hypothesizes that the identification and suppression of intra-species violence provided the basis for a human moral system and human behavior which gives man a competitive advantage (Boem, Journal of Consciousness Studies, Volume 7, Numbers 1-2, 2000, pp. 79-101 and Boehm Harvard University Press,1999, “Hierarchy in the forest: the evolution of egalitarian behavior.”). This hypothesis is supported by human-chimpanzee comparative studies by Richard W. Wrangham, Michael L. Wilson and Martin N. Muller (Primates, 2006) in which they explored the behavior of chimpanzees with particular emphasis on the rate of intra-species aggression between members of the same or different communities. They calculated that Chimpanzees have a rate of aggression similar to the first hunter-gatherer societies but a 2/3 folds higher aggression when compared with modern humans. These data partially support Boehms hypothesis: the reduction of violence between members of the   same species allows community to form and be in competitive advantages respect single individuals. Although humans show a reduced aggression between members of the same species, they are able of coalitional aggression to other groups for the survival of their own group: this is what we call war. Do our closest relatives make “war”? A 10 years study in the Ngogo  Kibale National Park, Uganda (where the Homo sapiens sapiens is involved in a intra-species inter-ethnic devastating war) by the naturalists John C. Mitani, David P. Watts, and Sylvia J. Amsler ( Current biology, Volume 20, Issue 12, 2010) showed that Chimpanzees are able to make lethal coalitional attacks on members of other groups for years (like battles) to finally occupy the region of the other groups (they basically win the “war”). Although the reasons for this kind of war are not entirely understood: “It is not sure whether the “coalitional attacks by Ngogo males may lead to new females joining their community” but all the evidences suggest that “By acquiring new territory through lethal coalitionaal attacks, male chimpanzees improve the feeding success of individuals in their own community, which in turn can lead to increased female reproduction”. From an evolutionary point of view this is particularly relevant.”

Although aggression within the same group is a competitive disadvantage  for the formation of a community (which, in general, represents a competitive evolutionary advantage for many “superior animals” such as wolves, penguins, but also for insects like ants and bees) inter-group aggression seems to be a common competitive evolutionary trait human beings and chimpanzees have in common.

In conclusion, these data suggest that aggression is something destructive and creative at the same time, creative when it is addressed externally (against other groups, other species etc.), destructive when it is infiltrates a community. Of course , externally directed aggression is destructive for the others and internal aggression is creative for a new group taking over the power but from the point of view of an organism-like community, this conclusion should be right, albeit very general.

The plasticity of Stem Cell

This diagram shows the hematopoiesis as it occ...

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There’s no better way than start our blog talking about the progenitors of all the cells in pluricellular living organisms: the Stem Cells

A recent paper by Szavo and colleagues described a protocol to obtain blood cells starting from skin fibroblast (the cells that produce extracellular matrix). It sounds like a science fiction tail but it is actually the result of many years of research that step by step, in different laboratories around the world, build up this technology. But let have a quick look at the recent evidences that brought to this discovery.

One of the most important challenges in medicine is the ability to regenerate an entire tissue or organ to replace the non-functional one, situation that can occur after numerous different injuries such as genetic disorder, cancer, stroke, multiple sclerosis, etc. This branch of medicine/biology research is called regenerative medicine. This field of study is based on the ability of  Stem Cells (multipotent/pluripotent progenitor cells) to proliferate and differentiate in many different types of cells such neurons, erythrocytes, muscle cells, etc (Dr Davide Torti will give soon a more general introduction about stem cell and the correlated principles). However, it is often very difficult to isolate a big number of pluripotent stem cell. It is therefore necessary to find innovative strategies to obtain them.

Isolating cells from embryos is an excellent approach to obtain a big number of high quality stem cells. Although using murine 8-cell embryos for research is commonly accepted, the use of human 8-cell embryos is still under ethical debate (Dr Mathias Zech will soon explore this issue). Conscious of the ethical limits, the scientific community moved on to define the adult pluripotent stem cells. These cells are present in the body of the adult individuals and they are responsible for the maintenance of our organs and tissues. The haematopoietic stem cells (HSC), which are present in the bone marrow and in the fetal cord blood, are the most known example. The HSC have been extensively used in the clinical environment: transplantation of bone marrow is still a fundamental treatment for patients affected by Leukemia.

The adult stem cells are often rare and difficult to isolate. Techniques, that allow to take a terminally differentiated cell (like fibroblast or neurons) and to invert its genetic program back to its progenitor and over to pluripotent cells, will overcome that limit. This is what has been done by Takahashi and Yamanaka (Nature 2006; http://www.ncbi.nlm.nih.gov/pubmed/16904174): using a retroviral vector (a viral vehicle for the transport of selected genes to be expressed within a target cell) they induced the expression of Oct3/4, Sox2, Klf4, and c-Myc genes (the so called Yamanaka factors) in fibroblasts. These factors triggered a genetic program in the target cells resulting in dedifferentiation of fibroblasts to pluripotent stem cells, thereafter called induced pluripotent stem cells (iPS). This was an astonishing result that finally confirmed what has been partially shown before by experiments of nuclear transfer into oocyte for cloning purpose: according to this technique it is possible to obtain a whole organism starting from its own differentiated/somatic cell. As shown in the scheme below, once the iPS are produced it is possible to obtain cells of different tissues by exposing them to cell-specific growth factors. This allows the production without theoretical limit of cells that can be used to regenerate patients’ organs in a patient-specific cell therapy way.

However some issues rise from the previous approach:

1) Feasibility: the protocol to obtain iPS cells is very laborious and still requires optimisation.

2) Biosafety: iPS can cause teratomas, an embryonic cancer that presents many tissues in the same tumour mass, typical of pluripotent cells when transplanted into mice.

In the attempt to solve these issues, first Vierbuchen et al and Ieda et al with murine cells and then Szabo et al. in human, demonstrated the possibility to directly induce fibroblasts to become blood cells without first inducing pluripotent stem cell-like status. Their researched started from the observation that while inducing iPS cells from fibroblast, a small proportion of intermediates express the protein CD45, a marker of haematopoietic cells. They also determine that the gene OCT4 was responsible for induction of Fibroblast CD45 positive (CD45+Fib).

The experimental design of this paper was as follow:

Therefore, Svabo and colleagues define an in vitro protocol for the induction of haematopoietic progenitor able to repopulate the peripheral blood population of sub-lethally irradiated immune-deficient mice.

Limits:

1)    They didn’t show the long-term repopulation ability of CD45+Fiboct4 in the in vivo model. The epigenetic status of the cell together with a limited telomerase activity may impact on their ability in surviving and to proliferate.

2)    The protocol requires 37 days to obtain haematopoietic cells. Quite long for clinical approach in which the viable cells number and the time to obtain them are 2 critical factors.

Do you observe any other limitations in this model? Which direction future research should take: direct differentiation (as shown by Svabo) or indirect differentiation (shown by Yamanaka)?