Macromolecular Structure
ABOUT
The Vertebrate Development and Regeneration group studies the mechanisms of cis-transcriptional regulation of genes and how mutations on non-coding cis-transcriptional regulatory sequences might impact in the development of some human diseases, in particular diabetes and pancreatic cancer. We employ genomic strategies to identify non-coding cis-transcriptional regulatory sequences and we perform genetic functional assays in zebrafish to evaluate the function of these sequences.
RESEARCH
Defining when, where and how much genes are transcriptionally expressed is one of the major mechanisms that control organogenesis and organ function. Variations in these mechanisms might contribute to disease. The transcriptional regulation of genes is achieved by non-coding cis-regulatory elements (CREs) spread over large genomic distances and is important for the proper development, function and homeostasis of organs. Our major research interest is to understand these mechanisms of transcriptional regulation. We use the zebrafish as a vertebrate model and we focus in the pancreas, our organ of choice.
Over the last years, we have developed methods to detect, validate and disrupt CREs. Among these tools, we have developed the Zebrafish Enhancer Detection vector, that contains an in vivo reporter to test cis-regulatory activity of sequences. We have also developed the Expression Disruption vector, that allows to disconnect CREs from their target genes. Combining these tools with genome wide approaches such as Assay for Transposase-Accessible Chromatin, Chromatin Immunoprecipitation and Circularized Chromosome Conformation Capture, we are uncovering CREs active in the pancreas and we are accessing their biological function by disturbing their activity. This information will be extremely relevant to clarify the role of CREs in the development of two major pancreatic diseases Diabetes and Pancreatic Cancer.
Team
Selected Publications
Isolation, cloning and structural characterization of boophilin, a multifunctional Kunitz-type proteinase inhibitor from the cattle tick. PLoS ONE3(2):1-17, 2008. [Journal: Article] [CI: 107]
DOI: 10.1371/journal.pone.0001624 SCOPUS: 45849130590
Figueiredo A., De Sanctis D., Gutiérrez-Gallego R., Cereija T., Macedo-Ribeiro S., Fuentes-Prior P., Pereira P.
Unique thrombin inhibition mechanism by anophelin, an anticoagulant from the malaria vector. Proceedings of the National Academy of Sciences of the United States of America109(52):E3649-E3658, 2012. [Journal: Article] [CI: 49] [IF: 9,7]
DOI: 10.1073/pnas.1211614109 SCOPUS: 84871839379
Santos J.A., Alonso-Garciá N., Macedo-Ribeiro S., Barbosa Pereira P.J.
The unique regulation of iron-sulfur cluster biogenesis in a Gram-positive bacterium. Proceedings of the National Academy of Sciences of the United States of America111(22):E2251-E2260, 2014. [Journal: Article] [CI: 36] [IF: 9,7]
DOI: 10.1073/pnas.1322728111 SCOPUS: 84901821729
Torreira E., Seabra A.R., Marriott H., Zhou M., Llorca O., Robinson C.V., Carvalho H.G., Fernández-Tornero C., Pereira P.J.B.
The structures of cytosolic and plastid-located glutamine synthetases from Medicago truncatula reveal a common and dynamic architecture. Acta Crystallographica Section D: Biological Crystallography70(4):981-993, 2014. [Journal: Article] [CI: 28] [IF: 2,7]
DOI: 10.1107/S1399004713034718 SCOPUS: 84898762319
Thompson R.E., Liu X., Ripoll-Rozada J., Alonso-García N., Parker B.L., Pereira P.J.B., Payne R.J.
Tyrosine sulfation modulates activity of tick-derived thrombin inhibitors. Nature Chemistry9(9):909-917, 2017. [Journal: Article] [CI: 80] [IF: 26,2]
DOI: 10.1038/NCHEM.2744 SCOPUS: 85028339870
Ripoll-Rozada J., Costa M., Manso J., Maranha A., Miranda V., Sequeira A., Rita Ventura M., Macedo-Ribeiro S., Pereira P., Empadinhas N.
Biosynthesis of mycobacterial methylmannose polysaccharides requires a unique 1-O-methyltransferase specific for 3-O-methylated mannosides. Proceedings of the National Academy of Sciences of the United States of America116(3):835-844, 2019. [Journal: Article] [CI: 7] [IF: 9,4]
DOI: 10.1073/pnas.1813450116 SCOPUS: 85060031004
Manso J.A., Nunes-Costa D., Macedo-Ribeiro S., Empadinhas N., Pereira P.J.B.
Molecular fingerprints for a novel enzyme family in actinobacteria with glucosamine kinase activity. mBio10(3):, 2019. [Journal: Article] [CI: 3] [IF: 6,8]
DOI: 10.1128/mBio.00239-19 SCOPUS: 85066245592
Cereija T.B., Alarico S., Lourenço E.C., Manso J.A., Ventura M.R., Empadinhas N., Macedo-Ribeiro S., Pereira P.J.B.
The structural characterization of a glucosylglycerate hydrolase provides insights into the molecular mechanism of mycobacterial recovery from nitrogen starvation. IUCrJ6:572-585, 2019. [Journal: Article] [CI: 4] [IF: 5,4]
DOI: 10.1107/S2052252519005372 SCOPUS: 85068320597
Hatos A., Hajdu-Soltész B., Monzon A.M., Palopoli N., Álvarez L., Aykac-Fas B., Bassot C., Benítez G.I., Bevilacqua M., Chasapi A., Chemes L., Davey N.E., Davidović R., Dunker A.K., Elofsson A., Gobeill J., Foutel N.S.G., Sudha G., Guharoy M., Horvath T., Iglesias V., Kajava A.V., Kovacs O.P., Lamb J., Lambrughi M., Lazar T., Leclercq J.Y., Leonardi E., MacEdo-Ribeiro S., MacOssay-Castillo M., Maiani E., Manso J.A., Marino-Buslje C., Martínez-Pérez E., Mészáros B., Mičetić I., Minervini G., Murvai N., Necci M., Ouzounis C.A., Pajkos M., Paladin L., Pancsa R., Papaleo E., Parisi G., Pasche E., Barbosa Pereira P.J., Promponas V.J., Pujols J., Quaglia F., Ruch P., Salvatore M., Schad E., Szabo B., Szaniszló T., Tamana S., Tantos A., Veljkovic N., Ventura S., Vranken W., Dosztányi Z., Tompa P., Tosatto S.C.E., Piovesan D.
DisProt: Intrinsic protein disorder annotation in 2020. Nucleic Acids Research48(D1):D269-D276, 2020. [Journal: Article] [CI: 211] [IF: 17]
DOI: 10.1093/nar/gkz975 SCOPUS: 85077666918
Agten S.M., Watson E.E., Ripoll-Rozada J., Dowman L.J., Wu M.C.L., Alwis I., Jackson S.P., Pereira P.J.B., Payne R.J.
Potent Trivalent Inhibitors of Thrombin through Hybridization of Salivary Sulfopeptides from Hematophagous Arthropods. Angewandte Chemie - International Edition60(10):5348-5356, 2021. [Journal: Article] [CI: 15] [IF: 16,8]
DOI: 10.1002/anie.202015127 SCOPUS: 85099868534
Calisto B.M., Ripoll-Rozada J., Dowman L.J., Franck C., Agten S.M., Parker B.L., Veloso R.C., Vale N., Gomes P., de Sanctis D., Payne R.J., Pereira P.J.B.
Sulfotyrosine-Mediated Recognition of Human Thrombin by a Tsetse Fly Anticoagulant Mimics Physiological Substrates. Cell chemical biology28(1):26-33.e8, 2021. [Journal: Article] [CI: 15] [IF: 9]
DOI: 10.1016/j.chembiol.2020.10.002 SCOPUS: 85097103852
