Difference between revisions of "Team:Valencia UPV/Components"

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<p>The aim of our magic lamp is to definitely improve the accessibility of urgent needed products to those places with lack of them. Although space and mars are the places with the greatest difficulties of access, we wanted to start first by improving our surrounding, we started in the earth. There are many organization in charge of compiling information about world health problems. The World Health Organization and UNICEF have great reports about the real problems in our world. In a 2004 report they evaluate the disease incidence according to the incomes of countries, which was very informative for our decision as usually accessibility is inversely correlated with incomes.  </p>
 
<p>The aim of our magic lamp is to definitely improve the accessibility of urgent needed products to those places with lack of them. Although space and mars are the places with the greatest difficulties of access, we wanted to start first by improving our surrounding, we started in the earth. There are many organization in charge of compiling information about world health problems. The World Health Organization and UNICEF have great reports about the real problems in our world. In a 2004 report they evaluate the disease incidence according to the incomes of countries, which was very informative for our decision as usually accessibility is inversely correlated with incomes.  </p>
 
 
 +
<p> <div style="text-align: center;"><img width=500em src="https://static.igem.org/mediawiki/2015/1/14/Valencia_UPC_deathsbyincome.png" usemap="#dnamap"></div> </p>
  
 +
        <p> <div style="text-align: center;"><h5><b>Figure 1. </b></h5></div> </p>
  
 +
<p>In 2004 the WHO proposed a plan for the reduction of this differences among income countries. The next table present the expected reduction for each type of disease among the next 30 years. However this table introduced the expected results for 2015, sadly the report of this year states that the estimated reduction has not been get. UNICEF in its global action plan for the prevention and control of pneumonia and diarrhea (GAPPD) has evaluated the accessibility of the treatment to the infants with this diseases and in some cases it does not reach even the 50% of those who really need it.</p>
 +
 +
<p> <div style="text-align: center;"><img width=500em src="https://static.igem.org/mediawiki/2015/d/d1/Valencia_UPC_lackofaccesibility.png" usemap="#dnamap"><img width=400em src="https://static.igem.org/mediawiki/2015/8/87/Valencia_UPC_drugsbyplace.png" usemap="#dnamap"></div>
 +
 +
</p>
 +
 +
        <p> <div style="text-align: center;"><h5><b>Figure 2. </b></h5></div> </p>
 +
 +
 +
       
 +
<p>Then it is clear that there’s a real health problem due to the lack of accessibility of the treatments. Those deaths are not caused by something we do not know how to fight, they are evitable deaths, and most of them affect infants under 5 years. That is why we decided to produce four different drugs capable to fight against this diseases in our magic lamp. </p>
 +
 +
<p>The first decision was something able to decrease the diarrhea disease which is the one with the highest number of affected patients in all countries. </p>
 +
 +
<p> <div style="text-align: center;"><img width=500em src="https://static.igem.org/mediawiki/2015/5/54/Valencia_UPC_drugsprevalency.png" usemap="#dnamap"></div> </p>
 +
 +
        <p> <div style="text-align: center;"><h5><b>Figure 4. </b></h5></div> </p>
 +
 +
<p>In the UNICEF plan against diarrhea (October 2009), one of the seven action points to drastically reduce the number of deaths is the introduction of rotavirus vaccine in Africa and Asia where the burden is greatest. They have estimated that about 40% of diarrhea cases are caused by rotavirus. Cholera is the other guest in this issue but we will treat it later.</p>
 +
 +
<p> <div style="text-align: center;"><img width=500em src="https://static.igem.org/mediawiki/2015/0/09/Valencia_UPC_diarrhea.png" usemap="#dnamap"></div> </p>
 +
 +
        <p> <div style="text-align: center;"><h5><b>Figure 4. </b></h5></div> </p>
 +
 +
<p>Then, introduction of a rotavirus vaccine will reduce to the half the cases of acute diarrhea. However as always it does not reach the poorest places that are the ones with greater need. In the 2012 report of UNICEF about diarrhea they insist about the importance of this vaccine and that it has not been implanted in the low income countries.</p>
 +
 +
 +
<p> <div style="text-align: center;"><img width=500em src="https://static.igem.org/mediawiki/2015/b/b7/Valencia_UPC_rotvaccine.png" usemap="#dnamap"></div> </p>
 +
 +
        <p> <div style="text-align: center;"><h5><b>Figure 4. </b></h5></div> </p>
 +
 +
<p>Our production of rotavirus vaccine is based in a Small Inmuno Protein (SIP). SIP construction consist in the variable region of a whole antibody with some part of its constant region. The main advantage for its production is that they are produced with just one transcript.</p>
 +
 +
<p> <div style="text-align:center;"><img width=300em src="https://static.igem.org/mediawiki/2015/d/d6/Valencia_UPC_IgG.png" usemap="#dnamap"><img width=300em src="https://static.igem.org/mediawiki/2015/5/50/Valencia_UPC_sip.png" usemap="#dnamap"></div>
 +
 +
 +
        <p> <div style="text-align: center;"><h5><b>Figure 4. </b></h5></div> </p>
 +
 +
<p>The SIP construction was performed by Juarez P (non published data), and kindly provided to us for our experiments. In the construction designed Juarez, used the variable regions obtained by them in a previous work (Juarez et al, 2013) in which analyzed the combinatorial expression of 16 inmunoglobulines against the rotavirus protein VP8 which is located in the capside region. The chosen variable region for the SIP was obtained from the combination with better activity against this epitope. This research group also demonstrated that those tomato expressing the sIgA presented the same composition than those wild type, so both were equally safe (Juarez et al, 2014). </p>
 +
 +
<p>Together with the rotavirus infection the other great cause of deaths in undeveloped countries and even more in infants ad it is shown in the UNICEF report of 2014, is the pneumonia. Being both of them the responsible of more than the 20% of children deaths.</p>
 +
 +
<p> <div style="text-align: center;"><img width=500em src="https://static.igem.org/mediawiki/2015/6/6c/Valencia_UPC_pneumony.png
 +
" usemap="#dnamap"></div> </p>
 +
 +
        <p> <div style="text-align: center;"><h5><b>Figure 4. </b></h5></div> </p>
 +
 +
<p>Natural response to infection in the lower respiratory tract depends mainly in the neutrophilic granulocyte which secret several products in order to fight infection. One of these products is lactoferrin, a glicosilated protein with two homologous domains able to interact with iron ions. It is the chelating property the one which gives this protein their bacteriostatic activity (Otto et al, 1992). The bactericidal activity resides in the N-lobe of the protein, it acts agains E.coli or V.cholerae among others. Oral administrationof lactoferrin has been prove to has antimicrobial but also antiviral activity in animals models (Teraguchi et al, 2004) increasing the levels of leukocytes and cytokines as interferon gamma, interleukin 12 and 18. It also stimulates the activity of macrophages, so lactoferrin plays an important role in pathogen eradication and homeostasis maintenance in episodes of infection.</p>
 +
 +
<p>Pneumonia major cause is the infection by Streptococcus pneumoniae, causing also meningitis, septicemia and otitis media (Butler Jc et al, 1999). Mirza Shaper et al, 2004, observed that lactoferrin apoprotein (without iron ions) has bactericidal activity. They also confirmed that this activity is maintained by just the first 11 amino acids of the N-terminous domain. The oral treatment of lactoferrin in animal models has demonstrated to attenuate pneumonia by decreasing the infiltration of inflamatpry cells in lung (Kouichirou et al, 2005). However, this treatment might not be sufficient since there are strains more resitent to apolactoferrin since they express a surface protein that inhibits the killing mediated by lactoferrin. Nevertheless the therapy can include antibodies against this surface protein (PspA) presenting synergic activity (Mirza Shaper et al,  2004).</p>
 +
 +
<p>An other public health concern is hepatitis. Dr Gottfried Hirnschall, the director of the WHO programme against this viral disease, states that one again the problem in is not the weapons, we know how to prevent, control and even cure some hepatitis types. There are 1.45 million death per year caused by hepatitis, in fact the 80% of deaths produced by liver failure are caused by type B and C. </p>
 +
 +
<p>However there is a particular disease that appear always after a natural catastrophe and in which is even more important the accessibility issue, it is the cholera.</p>
 +
 +
<p> <div style="text-align: center;"><img width=500em src="https://static.igem.org/mediawiki/2015/3/37/Valencia_UPC_cholera.png
 +
" usemap="#dnamap"></div> </p>
 +
 +
        <p> <div style="text-align: center;"><h5><b>Figure 4. </b></h5></div> </p>
  
 
<ul class="actions" style="text-align:right">
 
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<li><a href="https://2015.igem.org/Team:Valencia_UPV/" class="button alt">Components</a></li>
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<li><a href="https://2015.igem.org/Team:Valencia_UPV/" class="button alt">2</a></li>
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<li><a href="https://2015.igem.org/Team:Valencia_UPV/" class="button alt">Toggle Switches</a></li>
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<li><a href="https://2015.igem.org/Team:Valencia_UPV/" class="button alt">3</a></li>
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<li><a href="https://2015.igem.org/Team:Valencia_UPV/" class="button alt">Recombinases</a></li>
 
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Revision as of 22:19, 16 September 2015

Valencia UPV iGEM 2015

Components

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Toggle Switches

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Recombinases

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Drug production

The aim of our magic lamp is to definitely improve the accessibility of urgent needed products to those places with lack of them. Although space and mars are the places with the greatest difficulties of access, we wanted to start first by improving our surrounding, we started in the earth. There are many organization in charge of compiling information about world health problems. The World Health Organization and UNICEF have great reports about the real problems in our world. In a 2004 report they evaluate the disease incidence according to the incomes of countries, which was very informative for our decision as usually accessibility is inversely correlated with incomes.

Figure 1.

In 2004 the WHO proposed a plan for the reduction of this differences among income countries. The next table present the expected reduction for each type of disease among the next 30 years. However this table introduced the expected results for 2015, sadly the report of this year states that the estimated reduction has not been get. UNICEF in its global action plan for the prevention and control of pneumonia and diarrhea (GAPPD) has evaluated the accessibility of the treatment to the infants with this diseases and in some cases it does not reach even the 50% of those who really need it.

Figure 2.

Then it is clear that there’s a real health problem due to the lack of accessibility of the treatments. Those deaths are not caused by something we do not know how to fight, they are evitable deaths, and most of them affect infants under 5 years. That is why we decided to produce four different drugs capable to fight against this diseases in our magic lamp.

The first decision was something able to decrease the diarrhea disease which is the one with the highest number of affected patients in all countries.

Figure 4.

In the UNICEF plan against diarrhea (October 2009), one of the seven action points to drastically reduce the number of deaths is the introduction of rotavirus vaccine in Africa and Asia where the burden is greatest. They have estimated that about 40% of diarrhea cases are caused by rotavirus. Cholera is the other guest in this issue but we will treat it later.

Figure 4.

Then, introduction of a rotavirus vaccine will reduce to the half the cases of acute diarrhea. However as always it does not reach the poorest places that are the ones with greater need. In the 2012 report of UNICEF about diarrhea they insist about the importance of this vaccine and that it has not been implanted in the low income countries.

Figure 4.

Our production of rotavirus vaccine is based in a Small Inmuno Protein (SIP). SIP construction consist in the variable region of a whole antibody with some part of its constant region. The main advantage for its production is that they are produced with just one transcript.

Figure 4.

The SIP construction was performed by Juarez P (non published data), and kindly provided to us for our experiments. In the construction designed Juarez, used the variable regions obtained by them in a previous work (Juarez et al, 2013) in which analyzed the combinatorial expression of 16 inmunoglobulines against the rotavirus protein VP8 which is located in the capside region. The chosen variable region for the SIP was obtained from the combination with better activity against this epitope. This research group also demonstrated that those tomato expressing the sIgA presented the same composition than those wild type, so both were equally safe (Juarez et al, 2014).

Together with the rotavirus infection the other great cause of deaths in undeveloped countries and even more in infants ad it is shown in the UNICEF report of 2014, is the pneumonia. Being both of them the responsible of more than the 20% of children deaths.

Figure 4.

Natural response to infection in the lower respiratory tract depends mainly in the neutrophilic granulocyte which secret several products in order to fight infection. One of these products is lactoferrin, a glicosilated protein with two homologous domains able to interact with iron ions. It is the chelating property the one which gives this protein their bacteriostatic activity (Otto et al, 1992). The bactericidal activity resides in the N-lobe of the protein, it acts agains E.coli or V.cholerae among others. Oral administrationof lactoferrin has been prove to has antimicrobial but also antiviral activity in animals models (Teraguchi et al, 2004) increasing the levels of leukocytes and cytokines as interferon gamma, interleukin 12 and 18. It also stimulates the activity of macrophages, so lactoferrin plays an important role in pathogen eradication and homeostasis maintenance in episodes of infection.

Pneumonia major cause is the infection by Streptococcus pneumoniae, causing also meningitis, septicemia and otitis media (Butler Jc et al, 1999). Mirza Shaper et al, 2004, observed that lactoferrin apoprotein (without iron ions) has bactericidal activity. They also confirmed that this activity is maintained by just the first 11 amino acids of the N-terminous domain. The oral treatment of lactoferrin in animal models has demonstrated to attenuate pneumonia by decreasing the infiltration of inflamatpry cells in lung (Kouichirou et al, 2005). However, this treatment might not be sufficient since there are strains more resitent to apolactoferrin since they express a surface protein that inhibits the killing mediated by lactoferrin. Nevertheless the therapy can include antibodies against this surface protein (PspA) presenting synergic activity (Mirza Shaper et al, 2004).

An other public health concern is hepatitis. Dr Gottfried Hirnschall, the director of the WHO programme against this viral disease, states that one again the problem in is not the weapons, we know how to prevent, control and even cure some hepatitis types. There are 1.45 million death per year caused by hepatitis, in fact the 80% of deaths produced by liver failure are caused by type B and C.

However there is a particular disease that appear always after a natural catastrophe and in which is even more important the accessibility issue, it is the cholera.

Figure 4.