instituto de biologia molecular e celular | institute for molecular and cell biology
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Santos, Sofia Research Interest |
The experimental induced brain injury model that is currently under investigation is stroke. The tools to develop these studies are genetically modified mice using Cre/loxP technology to specifically ablate Rho GTPases - the most prominent target of the experimental project.
Projects as Principal Investigator
Funded by FCT: PTDC/SAU-BMA/118869/2010. Title: NSCgel- Molecularly-designed hydrogels for neural stem cell transplantation and axonal regeneration: a novel approach to create a permissible environment for regeneration in the spinal cord.
Supervision
Cansu Karabiyik (Master Student)
References
Santos SD, Lambertsen KL, Clausen B, Finsen B, Saraiva MJ. Transthyretin neuroprotection in a mouse model of brain ischemia. J Neurochem. 2010. 115: 1434-1444.
Barateiro A, Miron V, Santos SD, Relvas JB, Fernandes A, ffrench-Constant C, Brites D. Unconjugated bilirubin restricts oligodendrocyte differentiation and axonal myelination. Mol Neurobiol. 2012. 47: 632-644.
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Silvestre, Ricardo Research Interest |
My current objective is to elucidate how the modification of host cell metabolism and bioenergetics arising during the infection impact the immune functions (macrophage and dendritic cells) and by consequence the infection dynamics. A special emphasis is given to AMPK and sirtuin proteins as well as the implication of mitochondrial dynamics and biogenesis during infection. Currently, I am using Leishmania infantum as a cellular infection model, but at long-term other intracellular pathogens will be used to identify shared or individual new host pathways and functions exploited by pathogens.
Projects as Principal Investigator
Fundação para a Ciência e Tecnologia, Portugal, PTDC/CVT/110732/2009. Development of a new immunological screening method for leishmaniasis using colloidal gold nanoparticles.
Fundação para a Ciência e Tecnologia, Portugal, PTDC/SAU-FCF/100749/2008. Implication of sirtuin proteins in the regulation of antigen presenting cells apoptosis during leishmaniasis: a therapeutic approach.
Supervision
Ana Luísa Robalo (Master); Diana Raquel Bento Moreira (PhD student)
References
Moreira D, Santarém N, Loureiro I, Tavares J, Silva AM, Amorim AM, Ouaissi A, Cordeiro-da-Silva A, Silvestre R. Impact of continuous axenic cultivation in Leishmania infantum virulence. PLoS Negl Trop Dis. 2012 Jan;6(1):e1469
Resende M, Moreira D, Augusto J, Cunha J, Neves B, Cruz MT, Estaquier J, Cordeiro-da-Silva A and Silvestre R. Leishmania -infected MHCIIhigh dendritic cells polarize CD4 +T cells towards a non-protective T-bet+ IFN-γ + IL-10+phenotype. J Immunol 2013 Jul1;191(1):262-73
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Vale, Ana do Research Interest |
Currently, I’m very interested in the study of the intoxication mechanism used by the apoptogenic toxin AIP56 from Photobacterium damselae subsp. piscicida and in the structure-function relationship of the toxin.
Projects as Principal Investigator
Fundação para a Ciência e Tecnologia, Portugal, PTDC/BIA-MIC/3463/2012. Studies towards identification of structural determinants required for receptor binding and membrane translocation of AIP56, a Photobacterium damselae subsp. piscicida apoptogenic AB toxin targeting NF-kB
Supervision
Lilana Marisa Gonçalves Pereira (PhD student), Rute Daniela Pinto (Post-Doc), José Martinho Oliveira Peres (Master Student)
References
Silva DS, Pereira LMG, Moreira AR, Ferreira-da-Silva F, Brito RM, Faria TQ, Zornetta I, Montecucco C, Oliveira P, Azevedo JE, Pereira PJB, Macedo-Ribeiro S, do Vale A*, dos Santos NMS* (2013) The Apoptogenic Toxin AIP56 Is a Metalloprotease A-B Toxin that Cleaves NF-kb P65. PLoS Pathog 9(2): e1003128.doi:10.1371/ journal.ppat.1003128 (joint senior authors)
do Vale A, Costa-Ramos C, Silva A, Silva DSP, Gartnër, F, dos Santos, NMS, Silva, MT (2007). Systemic macrophage and neutrophil destruction by secondary necrosis induced by a bacterial exotoxin in a Gram-negative septicemia. Cell Microbiol 9(4), 988-1003.
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Duarte, Tiago Research Interest |
Our hypothesis that transcription factor Nrf2-mediated resistance to oxidative stress is a modifier of liver disease progression is being tested in experimental models of hemochromatosis and non-alcoholic fatty liver disease (NAFLD). The team will also investigate the contribution of iron towards hepatic fibrosis, and the therapeutic potential of natural or synthetic small-molecule Nrf2 activating compounds in liver disease.
Projects as Principal Investigator
Fundação para a Ciência e a Tecnologia, Portugal, PTDC/BIM-MET/0739/2012. “Understanding the contribution of iron overload in non-alcoholic fatty liver disease: identification of cellular players and potential molecular therapeutic targets”
Fundação para a Ciência e Tecnologia, Portugal, PTDC/SAU-FCF/101177/2008. “A role for Nrf2/ARE cytoprotective signalling in iron overload. Adaptive response to oxidative stress as a disease modifier in HFE associated hereditary hemochromatosis”
University of Porto, Portugal, PP_IJUP2011 122. “Is the cytoprotective Nrf2 signalling pathway induced in human blood monocytes from HFE hemochromatosis patients and is there an association with disease penetrance?”
References
Silva−Gomes, S., Santos, A. G., Caldas, C., Silva, C. M., Neves, J. V., Lopes, J., Carneiro, F., Rodrigues, P. N., Duarte, T. L. (2014) Transcription factor NRF2 protects mice against dietary iron-induced liver injury by preventing hepatocytic cell death. Journal of Hepatology, 60: 354-61.
Duarte TL, Cooke MS, Jones GDD. Gene expression profiling reveals new protective roles for vitamin C in human skin cells. Free Radical Biol Med 2009 46:78–87
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Mendes, Marta Vaz Research Interest |
At the present, our work focus on (i) the oxidative stress based regulation of Streptomyces spp. secondary metabolism and morphological differentiation, and (ii) the crosstalk of redox-based signaling with other secondary metabolism regulatory networks such as iron and phosphate metabolism. The ultimate goal is the knowledge-based optimization of microbial processes.
Projects as Principal Investigator
ERA-IB and Fundação para a Ciência e Tecnologia, Portugal, ERA-IB/0001/2010. ROBUST FERMENTATION PRODUCTION OF TACROLIMUS AND RELATED IMMUNOSUPPRESSORS: MOLECULAR GENETICS AND METABOLIC ENGINEERING TO CONSTRUCT A BY-PRODUCT FREE SUPERPRODUCER.
Supervision
Tiago Beites (Post-doc), Sílvia Pires (PhD student), Rute Oliveira (Research Fellow), Rui Silva (MSc Student).
References
Beites T, A Rodríguez-García, F Santos-Beneit, H Osório, P Moradas-Ferreira, JF Aparicio & MV Mendes. Genome-wide analysis of the regulation of pimaricin production in Streptomyces natalensis by reactive oxygen species. Appl Microbiol Biotechnol. 2014, DOI: 10.1007/s00253-013-5455-z.
Beites T, SD Pires, CL Santos, H Osório, P Moradas-Ferreira & MV Mendes. Crosstalk between ROS homeostasis and secondary metabolism in Streptomyces natalensis ATCC 27448: Modulation of pimaricin production by intracellular ROS. 2011, PLoS ONE, 6(11): e27472.
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Monteiro, Joana Paes de Faria Research Interest |
Projects as Principal Investigator
Fundação para a Ciência e Tecnologia, Portugal, PTDC/SAU-NEU/099007/2008. TITLE: “Understanding the role of the axon/glia functional unit during developmental myelination and in remyelination”
References
Thurnherr T., Benninger Y., Wu X., Chrostek A., Krause S.M., Nave K.A., Franklin R.J., Brakebush C., Suter U., Relvas J.B. Cdc42 and Rac1 signaling are both required for and act synergistically in the correct formation of myelin sheaths in the CNS. J Neurosci 26:10110-9
Benninger Y., Colognato H., Thurnherr T., Franklin R.J., Leone D.P., Atanasoski S., Nave K.A., Ffrench-Constant C., Suter U., Relvas J.B. Beta1-integrin signaling mediates premyelinating oligodendrocyte survival but is not required for CNS myelination and remyelination. J Neurosci 26:7665-73
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Pinto, Manuel Research Interest |
We focus on the enzymes that ensure the transient nature of such modifications, by removing ubiquitin or SUMO from modified proteins (DUBs and SENPs, respectively). Our aim is to characterize these enzymes and define their structure, substrates and interaction network.
Projects as Principal Investigator
FCT project EXPL/BEX-BCM/0320/2012, "Understanding the biological role of SUMO proteases".
Supervision
Andreia Vilar Mendes (Master Student)
References
Pinto, M.P., Carvalho, A.F., Grou, C.P., Rodríguez-Borges, J.E., Sá-Miranda, C. and Azevedo J.E. (2012). Heat shock induces a massive but differential inactivation of SUMO-specific proteases. Biochim. Biophys. Acta. 1823, 1958-66.
Grou, C.P., Francisco, T., Rodrigues, T.A., Freitas, M.O., Pinto, M.P., Carvalho, A.F., Domingues, P., Wood, S.A., Rodríguez-Borges, J.E., Sá-Miranda, C., Fransen, M. and Azevedo J.E. (2012). Identification of Ubiquitin-specific Protease 9X (USP9X) as a Deubiquitinase Acting on Ubiquitin-Peroxin 5 (PEX5) Thioester Conjugate. J. Biol. Chem. 287, 12815-27.
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Valentim, Ana Research Interest |
This has clinical (human and animal) and research implications because anaesthesia may be an unexpected variable of an experiment, compromising research results. I'm specially interested in evaluating the cognitive effects of anaesthesia from a phenotypic perspective, using behavioural tasks, and complementing these results using a multi-disciplinary approach. This kind of study in laboratory animals will refine anaesthesia used in research, and improve animal welfare. Furthermore, it is also indicative of the effects of anaeshetics in medical practise.
Projects as Principal Investigator
FCT, PTDC/CVT-WEL/4672/2012, Zebrafish ( Danio rerio) anaesthesia and potential implications in research – reduction, replacement and refining techniques/procedures
References
Valentim A., Di Giminiani P., Ribeiro P., Rodrigues P., Olsson I. A., Antunes L. Lower isoflurane concentration affects spatial learning and neurodegeneration in adult mice compared with higher concentrations. Anesthesiology 2010 113:1099-1108.
Valentim A.M, Ribeiro P.O., Olsson I.A., Antunes L.M. The memory stages of a spatial Y-maze task are not affected by a low dose of ketamine/midazolam. European Journal Pharmacology 2013 15;712(1-3):39-47.
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Pinto, Jorge
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Tavares, Lígia Research Interest |
I have a strong background in epigenetics that help me to understand which changes occur at the DNA level that can silence or induce the expression of certain genes. Currently I’m studying signalling pathways to lear about how the extracellular environment send signals to the cell. For that I’m studying the role of integrins and RhoGTPases in glia using the Drosophila eye imaginal disc as a model. In the future I hope to combine both areas of research.
Projects as Principal Investigator
FCT, EXPL/NEU-NMC/0380/2012, Identification of new players of Rho 1 signalling pathway involved in delivering Rho1 message in the nucleus
References
Tavares, L., Dimitrova, E., Oxley, D., Webster, J., Poot, R., Demmers, J., Bezstarosti, K., Taylor, S., Ura, H., Koide, H., et al. RYBP-PRC1 Complexes Mediate H2A Ubiquitylation at Polycomb Target Sites Independently of PRC2 and H3K27me3. Cell (2012) 148, 664-678
Landeira D, Sauer S, Poot R, Dvorkina M, Mazzarella L, Jørgensen HF, Pereira CF, Leleu M, Piccolo FM, Spivakov M, Brookes E, Pombo A, Fisher C, Skarnes WC, Snoek T, Bezstarosti K, Demmers J, Klose RJ, Casanova M, Tavares L, Brockdorff N, Merkenschlager M, Fisher AG. Jarid2 is a PRC2 component in embryonic stem cells required for multi-lineage differentiation and recruitment of PRC1 and RNA Polymerase II to developmental regulators. Nat Cell Biol. (2010) 12, 618-24.
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Almeida, Rosário Research Interest |
We approach the study of amyloidosis through in vitro studies of transthyretin aggregation and amyloid fibril formation, and search for physiologic and therapeutic modulators of these processes through in vivo studies, using mice models for transthyretin amyloidosis, in particular for familial amyloidotic polyneuropathy (FAP). We also investigate the effects of several natural and synthetic compounds as inhibitors of transthyretin amyloidosis and their potential use as therapeutic agents for the disease.
Projects as Principal Investigator
«Search for TTR ligands modulators of amyloidogenesis» - POCI/SAU-MMO/57321/2004 (01/06/2005-31/08/2008)
«Study of natural and synthetic inhibitors of transthyretin amyloidosis and characterization of their mechanism of action» - PTDC/SAU-ORG/116645/2010 (01/03/2012- 31/08/2014)
Supervision
Nelson Gomes Ferreira (Post-Doc), Alda Henriques (Research Fellow), Beatrice Bettochi (Master Student), Ana Isabel Almeida (graduation student).
References
Ferreira N, Pereira-Henriques A, Attar A, Klärner FG, Schrader T, Bitan G, Gales L, Saraiva MJ, Almeida MR. Molecular Tweezers Targeting Transthyretin Amyloidosis. Neurotherapeutics. 2014 Jan 24. [Epub ahead of print] PubMed PMID: 24459092.
Ferreira N, Santos SA, Domingues MR, Saraiva MJ, Almeida MR. Dietary curcumin counteracts extracellular transthyretin deposition: insights on the mechanism of amyloid inhibition. Biochim Biophys Acta – Molecular Basis of Disease, 2013; 1832(1):39-45.
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Lima, Maria Manuela Medeiros Research Interest |
Our focus of research is Machado-Joseph disease (DMJ; MIM #109150; ORPHA98757), which is the second most frequent poly-Q disease, reaching in the Azores islands the highest prevalence worldwide. Our ongoing project is based on results from a whole-genome expression study using a cDNA array, which has allowed us to establish a transcriptional profile of MJD. Several important pathways are being analyzed and novel potential biomarkers will be proposed in the context of the ongoing investigation.
Projects as Principal Investigator
FCT. PTDC/DTP-PIC/0370/2012. Title: MESCA3 – Molecular Endpoints in Machado-Joseph disease (MJD/SCA3): evaluation of transcriptional biomarkers in peripheral blood
Supervision
Amanda Ramos (Post-doc), Maria Teresa Cymbron (Post-doc), Nadyia Kazachkova (Post-doc), Mafalda Raposo (PhD Student), Paula Lourenço (PhD Student), Balbina Teixeira (Master Student).
References
BETTENCOURT C., RAPOSO M., KAZACHKOVA N., CYMBRON T., SANTOS C., KAY T., VASCONCELOS J., MACIEL P., DONIS K.C., PEREIRA M.L.S., JARDIM L.B., SEQUEIROS J. & M. LIMA (2011). The ε2 allele of APOE increases the risk of earlier age-at-onset in Machado-Joseph Disease (MJD/SCA3). Archives of Neurology, 68(12):1580-3. Impact Factor (JCR® 2010: 7.108)
BETTENCOURT, C. & M. LIMA (2011). Machado-Joseph Disease: from first descriptions to new perspectives. Orphanet Journal of Rare diseases, 6(1): 35 (JRC©2010: 5,825).
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Macedo, Fátima Research Interest |
Studies in LSD animal models and in LSD patient samples are being conducted. The immunological data are being integrated with the genetic, biochemistry and clinical presentation of the patients.
Projects as Principal Investigator
2011-2014 “Cross-talk between the pathogenic mechanisms of Lysosomal Storage Diseases and the lipid antigen presentation.” FCT PTDC/SAU-ORG/110112/2009
Supervision
Cátia Sofia Pereira (PhD student); Ana Filipa Dias (PhD student); Nuno Lopes (Master student); Maria da Luz Maia (Research assistant)
References
Pereira CS, Azevedo O, Maia ML, Dias AF, Sa Miranda MC, Macedo MF. Invariant Natural Killer T cells are phenotypically and functionally altered in Fabry disease. Mol Genet Metab. 2013doi:10.1016/j.ymgme.2013.01.018
Macedo MF, Quinta R, Pereira CS, Sa Miranda MC. Enzyme replacement therapy partially prevents invariant Natural Killer T cell deficiency in the Fabry disease mouse model. Mol Genet Metab. 2012; 106 (1): 83-91.
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Brites, Pedro Research Interest |
We are particularly interested in the role that ether-phospholipids play in membrane processes including axon growth, synapse formation and myelin synthesis. Using model organisms, we combine in vivo and in vitro studies to integrate physiological cell processes with disease states.
Projects as Principal Investigator
European Leukodystrophy Association – Research Foundation "Developing, characterizing and rescuing animal models of leukodystrophies: role of plasmalogen in mitigating oxidative stress".
Universidade do Porto, Projecto Pluridisciplinar 2011-33, “Computational vision applied to the segmentation and morphometric characterization of nerve histology in microscopic images”
Supervision
Tiago Silva (PhD student), Ana Rita Malheiro (PhD student).
References
P. Brites, P. Mooyer, L. el Mrabet, H. R. Waterham, and R.J. Wanders. Plasmalogens participate in very-long-chain fatty acid-induced pathology. Brain, 2009, 132(2):482-492.
S. Ferdinandusse, A. Zomer, J. C. Komen, C. van den Brink, M. Thanos, F. Hamers, R. J. A. Wanders, P. van der Saag, B.T. Poll-The, and P. Brites. (2008) Ataxia with Loss of Purkinje Cells in a Mouse Model for Refsum Disease. Proc. Natl. Acad. Sci. USA, 2008,105(46):17712-17717.
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Carvalho, Ana Research Interest |
The molecular underpinnings of cytokinesis remain poorly understood and elucidating them is of significance for the understanding of tumorigenesis. In addition, knowledge about the molecular basis of cytokinesis will likely translate to other essential cellular processes that also utilize contractile networks composed of actin and myosin II, namely muscle contraction, tissue morphogenesis, cell migration, cell invasion, wound healing, and endocytosis.
Our research focuses in the study of the structural organization and dynamics of the contractile ring, the filamentous structure of actin and myosin that drives cytokinesis. The experimental approaches that we use in the lab include live cell imaging, laser microsurgery, electron microscopy, and biochemistry and our experimental system is the nematode C. elegans.
Projects as Principal Investigator
Foundation for Science and Technology of Portugal (PTDC/BEX-BCM/0654/2012) - Actin and myosin II in the contractile ring - mechanisms of constriction
Supervision
Ana Marta Silva (Post-doc), Fung-Yi Chan (Post-doc), Daniel Osório (Post-doc), Joana Sousa (Trainee), Joana Saramago (MSc student).
References
Carvalho A, Olson S, Gutierrez E, Zhang K, Noble L, Zanin E, Desai A, Groisman A and Oegema K. Acute drug treatment in the early C. elegans embryo. PLoS ONE. 2011. 6(9): e24656
Carvalho, A., Desai, A. & Oegema, K. Structural memory in the contractile ring makes the duration of cytokinesis independent of cell size. Cell. 2009. 137, 926-937.
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Freitas, Renata Research Interest |
She is also interested to explore how changes in those mechanisms lead to birth defects in humans. Most of her research was conducted under the paradigmatic question of how locomotory structures appeared and evolved in vertebrates. Pursuing this topic, she is currently studying developmental pathways associated with HoxD genes, which are transcription factors strongly involved in limb morphogenesis and patterning. These questions are being addressed using mainly zebrafish as model organism and combining functional genomics and developmental biology approaches.
Projects as Principal Investigator
FCT: EXPL/BEX-BID/0801/2013. Shaping animal design: role of Hoxd13 target genes in the development of vertebrate limbs.
References
Freitas R, Zhang G, Cohn MJ. Evidence that mechanisms of fin development evolved in the midline of early vertebrates. Nature. 2006 Aug 31;442(7106):1033-7. Epub 2006 Jul 26.
Freitas R, Gómez-Marín C, Wilson JM, Casares F, Gómez-Skarmeta JL. Hoxd13 contribution to the evolution of vertebrate appendages. Dev Cell. 2012 Dec 11;23(6):1219-29. doi: 10.1016/j.devcel.2012.10.015.
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Sá, Eurico Research Interest |
Tight regulation of epithelial architecture is essential during embryonic development and to maintain homeostasis of adult organs. In fact, defects in proliferation and apico-basal polarity are an underlying cause of cancer in epithelial tissues, which are the source of most malignant tumors. The molecular organization of epithelial polarity and the mechanisms that ensure correct chromosome segregation are well studied, but how these processes are synchronized to maintain epithelial integrity during proliferation remain rather unexplored. We therefore aim to understand the link between the regulation of cell division and the organization of polarity at the tissue level, and to address the interplay between these processes in tumorigenesis.
Projects as Principal Investigator
Fundação para a Ciência e Tecnologia, Portugal, PTDC/BIA-BCM/120132/2010: Understanding the coordination between mitosis and cell polarity
Supervision
Sofia Moreira (BI fellow), Guilherme Ventura (Trainee).
References
Morais-de-Sá, E. and Sunkel, C. (2013). Adherens junctions determine the apical position of the midbody during follicular epithelial cell division. EMBO Rep 14, 696-703.
Morais-de-Sá, E., Mirouse, V., and St Johnston, D. (2010). aPKC phosphorylation of Bazooka defines the apical/lateral border in Drosophila epithelial cells. Cell 141, 509-523.
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Sousa, Sandra Research Interest |
To infect cells, bacterial pathogens developed molecular weapons that mimic host proteins and functions subverting classic signalling pathways. Using Listeria monocytogenes as a tool, we are studying new functions of host cytoskeleton components and characterizing new regulatory mechanisms relevant in the context of infection and in basic cell biology processes.
Projects as Principal Investigator
Fundação para a Ciencia e a Tecnologia, Portugal, PTDC/BIA-BCM/111215/2009. “Unravelling the interplay between Listeria monocytogenes infection and the host cell cycle.” (2011-2014)
European Society of Clinical Microbiology and Infectious Diseases (ESCMID), Basel, Switzerland. “Novel interfaces during host responses to pore forming toxins: crosstalk between ER chaperones and cytoskeletal proteins.” (2014-2016)
Supervision
Maria Teresa Almeida (PhD Student), Rui Filipe Cruz (PhD Student), Cláudia Brito (PhD Student), Ana Catarina Costa (Post-doc), Paulo Cunha (Post-doc).
References
Leitão E, Costa AC, Brito C, Costa L, Pombinho R, Cabanes D, Sousa S. Listeria monocytogenes induces host DNA damage and delays the host cell cycle to promote infection. Cell Cycle. 2014. In press.
Martins M, Custodio R, Camejo A, Almeida MT, Cabanes D, Sousa S. Listeria monocytogenes triggers the cell surface expression of Gp96 and interacts with its N-terminus to support cellular infection. J Biol Chem. 2012 Dec 14; 287(51):43083-93.
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Tavares, Joana Research Interest |
Light is being shed on a number of processes used by Plasmodium to successfully infect the host. By combining live imaging techniques and transgenic parasites, we are interested into dissect the molecular basis of sporozoites homing to the liver and the contribution of the liver during pre-erythrocytic phase as a lymphoid organ.
Projects as Principal Investigator
FCT. EXPL/JTAVARES-IF/00881/2012/CP0158/CT0005 Intravital imaging of Plasmodium liver infection.
FCT and FEDER. EXPL/IMI-MIC/1331/2013 and FCOMP-01-0124-FEDER-041854. Dissecting the molecular basis of the arrest of Plasmodium sporozoites in the liver sinusoids.
Supervision
Ines Loureiro (PhD student), Helena Ribeiro (Research fellow).
References
Tavares J, Formaglio P, Thiberge S, Mordelet E, Van Rooijen N, Medvinsky A, Ménard R, Amino R. Role of host cell traversal by the malaria sporozoite during liver infection. J Exp Med 2013, 210:905-15.
Gueirard P, Tavares J, Thiberge S, Bernex F, Ishino T, Milon G, Franke-Fayard B, Janse CJ, Ménard R, Amino R. Development of the malaria parasite in the skin of the mammalian host. Proc Natl Acad Sci USA 2010, 107: 18640-5.
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