Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

EVGN Zebrafish platform boosts European research on cardiovascular disease

13.09.2006
A new technological European Vascular Genomics Network (EVGN), Zebrafish platform is now fully operative at The FIRC Institute of Molecular Oncology Foundation (IFOM, http://www.ifom-firc.it, http://www.ifom-ieo-campus.it). The platform was launched at the beginning of this year by EVGN (a Network of Excellence focused on vascular biology and cardiovascular disease funded by the European Commission under the 6th Framework Programme; http://www.evgn.org; http://www.evgnvascularscience.org/english/index.php) and is conceived as a facility to be shared by EVGN members and partner laboratories. Its aim is to expand the scientific and clinical research in the field of Cardiovascular Diseases.

The facility is led by EVGN member Marina Mione, IFOM scientist and leader of the Zebrafish group. Developed after an IFOM proposal to the consortium, the technological platform will provide EVGN members with the possibility to test and validate in this unique in vivo system data previously obtained in vitro. Funding comes from EVGN and it covers an initial period of 2 years (with 60.000€/yr). At present, there are 5 ongoing collaborative projects involving EVGN partner laboratories from Italy, Germany, Finland, U.K. and France, whose completion is expected in one or two years.

WHY ZEBRAFISH?

Zebrafish (Danio rerio) is an ideal low-cost powerful model widely used for screening the angiogenic and cardiovascular regenerative properties of novel genes, for the validation of new drugs and drug targets and for the investigation of other human diseases (neurodegenerative diseases, osteoarthritis etc.). This is not surprising, as this model organism is endowed with an immune system, and fully functional nervous and cardiovascular systems. Besides, many human genes have an equivalent in Zebrafish and a number of biochemical pathways are similar between fish and men, albeit the two species are distant.

Easy to grow, the individuals become sexually mature at three months and the females lay up to 300 eggs per mating. The most interesting feature, however, is represented by the eggs themselves, which are transparent and allow the direct observation of inner events. “For this reason – points out IFOM scientist Marina Mione - this system is particularly suitable to observe any experimental modification, especially those that involve the early steps of the vascular system’s development”.

UNVEILING ANGIOGENESIS

Angiogenesis, the blood vessels growth that occurs during embryogenesis or after myocardial infarction and stroke, is a complex event. During its physiological course it is precisely modulated at the genetic level. However, there are times where it would be desirable to modulate this process at will: boosting it after an ischemic event that leaves tissues without oxygen, or dimming it in tumours that sprout their own vessels to nourish themselves. In both cases, Zebrafish proves to be the ideal model system for hypothesis testing and validation.

“The rapid life cycle of Zebrafish together with eggs’ transparency – confirms Marina Mione – are two of the most interesting features of this organism. They allow real time screening of any introduced modification and are especially useful when it comes to the analysis of the vascular development. Blood vessels growth starts early but Zebrafish needs functional vessels only after several days, since the embryo is vital even in the absence of a fully formed vascular system. This is a clear advantage over other experimental systems. We can monitor what happens whether blood vessels are defective, follow their anomalous growth and correlate any visible alteration to the mutation we introduced.”

Investigations carried out in Mione’s laboratory include the generation of transgenic Zebrafish to observe directly cell behaviour during vasculogenesis (de novo vessel formation) and angiogenesis (vessel sprouting), the suppression of a gene of interest (technically called knock-down) as well as the rescue of an original character. “Loss- and gain-of-function experiments are part of so-called reverse genetics”, says Mione. “They are easy to perform in Zebrafish and very informative, since they provide critical information for the study of candidate genes”. In gain-of-function experiments scientists ask what would happen if a specific gene is activated in the embryo where it is not normally active, whereas in loss-of-function experiments, they ask what happens when a particular function is removed from the embryo altogether.

The experiment design starts in one EVGN institution where initial data are gathered from in vitro systems; then Mione and colleagues carry out in vivo assays to confirm the hypotheses. Hence the collaborative effort between the partners helps to provide complete answers to asked questions. Among the projects that Mione is following, there is a study carried out in collaboration with the EVGN laboratory directed by Seppo Ylä-Herttuala, at the Department of Biotechnology and Molecular Medicine, A.I.Virtanen Institute, University of Kuopio, Finland. "We are studying vasculogenesis – says Kati Pulkkinen, who works in Seppo Ylä-Herttuala's laboratory in Kuopio – using a technique called knockdown morpholinos, to inactivate genes in a selective way. Our experiments are at an early stage. But results are coming, and we are in the middle of confirming them.

“Another important part of our research – says Mione – is the definition of the molecular mechanisms that govern angiogenesis during tumour growth, as well as the selection of antiangiogenic drugs”. To this purpose, fluorescence vascularization tests in Zebrafish are extremely useful because they allow to unveil the involvement of some genes in the angiogenesis of tumours, and to screen drugs potentially able to stop the process.

Angiogenesis, drug screening and drug targeting are some of the most important issues EVGN scientists are focussing on. This is why the newly established Zebrafish platform has been welcomed with much enthusiasm, as it is expected to give meaningful contribution to the understanding of the process and to suggest new strategies to modulate it at clinical level.

“Recent studies – observes Alain Tedgui, EVGN Scientific Coordinator from INSERM U689 in Paris - indicate that using Zebrafish we can investigate not only the molecular mechanisms of development, but also the cellular and molecular physiology and pathology in the adult. In the context of EVGN, cardiovascular pharmacology and angiogenesis are certainly the two areas in which we can expect fruitful findings. A potential limitation of this model system is that, so far, there is no report that atherosclerosis develops in Zebrafish vessels. However, it may be just a question of time to be able to do so!”

The European Vascular Genomics Network (EVGN) is a network of excellence funded by the European Commission under the 6th Framework Programme "Life Science, genomics and biotechnology for Health", aiming at integrating and strengthening the European research area in the field of Cardiovascular Diseases (Contract Number: LSHM-CT-2003-503254). Additional information on the EVGN is available at http://www.evgn.org/

Francesca Noceti | alfa
Further information:
http://www.evgn.org

Further reports about: Angiogenesis Cardiovascular EVGN Mione blood vessel molecular mechanism vascular

More articles from Life Sciences:

nachricht Rainbow colors reveal cell history: Uncovering β-cell heterogeneity
22.09.2017 | DFG-Forschungszentrum für Regenerative Therapien TU Dresden

nachricht The pyrenoid is a carbon-fixing liquid droplet
22.09.2017 | Max-Planck-Institut für Biochemie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: The pyrenoid is a carbon-fixing liquid droplet

Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.

A warming planet

Im Focus: Highly precise wiring in the Cerebral Cortex

Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.

The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...

Im Focus: Tiny lasers from a gallery of whispers

New technique promises tunable laser devices

Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...

Im Focus: Ultrafast snapshots of relaxing electrons in solids

Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!

When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...

Im Focus: Quantum Sensors Decipher Magnetic Ordering in a New Semiconducting Material

For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.

Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

I-ESA 2018 – Call for Papers

12.09.2017 | Event News

EMBO at Basel Life, a new conference on current and emerging life science research

06.09.2017 | Event News

 
Latest News

Rainbow colors reveal cell history: Uncovering β-cell heterogeneity

22.09.2017 | Life Sciences

Penn first in world to treat patient with new radiation technology

22.09.2017 | Medical Engineering

Calculating quietness

22.09.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>