Maria Arménia Carrondo Lab

	The Structural Genomics Laboratory studies proteins involved in diverse biological processes, such as DNA repair and protection, oxidative stress resistance and hydrogen sulfide metabolism, by a structural genomics approach. The lab combines structural biology methodologies like X-ray crystallography and Small Angle X-ray Scattering (SAXS), with X-ray imaging, biochemical, biophysical and spectroscopic analysis. Moreover, we are also building our knowledge on Cryo-Electron Microscopy through the Twining Project Horizon 2020 IMpaCT. The Laboratory is composed of three research teams which are integrated in the MOSTMICRO and iNOVA4Health Research Units at ITQB NOVA.
	Maria Arménia Carrondo Professor Catedrático CV PhD in Chemical Crystallography, Imperial College of Science and Technology, University of London, UK. Phone (+351) 214469657 | Extension 1657 Email carrondo@itqb.unl.pt| Lab website

Research Interests

The main goal of the Structural Genomics Group is to study proteins involved in DNA repair and protection, oxidative stress resistance, and hydrogen sulfide metabolism. The target proteins under study originate from prokaryotic and eukaryotic (unicellular to human) organisms. The research strategy aims at gaining a deeper understanding of microbial-to-human physiology and exploring the biotechnological and pharmacological potential of the studied protein targets.

The DNA repair studies aims to improve the current understanding of molecular mechanisms underlying Base Excision Repair (BER). A majority of our model enzymes are isolated from extremophiles and pathogens (e.g. D. radiodurans and A. salmonicida). Thus another goal is to reveal the organisms’ ability to maintain their genomes upon exposure to extreme environments like high doses of ionising radiation and ROS attacks by host organisms. Furthermore we are studying enzymes of marine origin with potential for commercial exploitation. 

We are also interested in understanding how prokaryotic organisms deal with oxidative stress. Currently, we are studying the molecular mechanisms associated with non-enzymatic systems involving small complexes of manganese-phosphate in radiation resistant bacteria but also enzymatic systems involved in the detoxification of reactive oxygen species and reduction of oxygen or nitric oxide. Our focus has been on proteins which protect DNA under stress conditions (Dps), rubrerythrins and flavodiirons proteins. The aim is to unravel the molecular and structural mechanisms of the target proteins integrated at cellular level and correlate with the intracellular metal homeostasis.

The human enzymes involved in hydrogen sulfide (H2S) metabolism (biosynthesis and breakdown) are being studied from a functional and structural viewpoint. Complementary to a deeper understanding of these enzymes within human (patho)physiology, an active search for compounds (natural, synthetic and FDA-approved drugs) with potential to modulate their activity is underway, combining several biophysical and biochemical methodologies. Another research line focuses on unique enzymes involved in microbial bioenergetics and sulfur amino acid metabolism, as potential drug targets for the development of next-generation antimicrobial drugs.

Group Members

Moe Team - DNA Repair

• Elin Moe, Researcher
• Andreia Fernandes, PhD Student (co-supervision with Prof. Maria Arménia Carrondo)
• Filipe Rollo, PhD Student (co-supervision with Dr. Smilja Todorovic)

Romão Team – DNA protection and Oxidative Stress Resistance

• Célia Romão, Researcher
• Sara Silva, Post-Doc
• Liliana Silva, PhD Student (co-supervision with Dr. Lígia Saraiva)
• André Gouveia, BI Fellow
• Fábio Rodrigues, BI Fellow

• Rafael Cavém Soares, Master Student in Biotechnology for Sustainability (in collaboration with Dr. Isabel A. Abreu)

• Guilherme Martins, Degree Thesis, Undergraduate student

• Catarina Cavaleiro, Undergraduate student

• Lucas Cardoso, Undergraduate student  

Vicente Team - Human hydrogen sulfide metabolism

• João B. Vicente, Assistant Researcher (FCT Investigator)

• Dalila Fernandes, PhD Student (co-supervision with Dr. Sofia Pereira, CEDOC and Dr. Pedro Matias, ITQB)

• Dalila Fernandes, PhD Student (co-supervision with Dr. Sofia Pereira, CEDOC and Dr. Pedro Matias, ITQB)
• Hana Pavlu-Pereira, PhD Student (co-supervision with Prof. Isabel Rivera, Faculty of Pharmacy, University of Lisbon)

Selected Publications 

1. Sarre A., Stelter M., Rollo F., De Bonis S., Seck A., Hognon C., Ravanat J.L., Monari A., Dehez F., Moe E., Timmins J. (2019) The three Endonuclease III variants of Deinococcus radiodurans possess distinct and complementary DNA repair activities. DNA Repair (Amst) 78:45-59. doi: 10.1016/j.dnarep.2019.03.014.

2. Santos S.P., Yang Y., Rosa M.T.G., Rodrigues M.A.A., Bouthier De La Tour C., Sommer S., Teixeira M., Carrondo M.A., Cloetens P., Abreu I.A., Romão C.V. (2019) The interplay between Fe and Mn in Deinococcus radiodurans triggers cellular protection during oxidative stress, Sci Rep 9: 17217. doi: 10.1038/s41598-019-53140-2

3. Zuhra K., Sousa P.M.F., Paulini G., Lemos A.R., Kalme Z., Bisenieks I., Bisenieks E., Vigante B., Duburs G., Bandeiras T.M., Saso L., Giuffrè A., and Vicente JB (2019) Screening Pyridine Derivatives against Human Hydrogen Sulfide-synthesizing Enzymes by Orthogonal Methods, Sci Rep 9(1): 684. doi: 10.1038/s41598-018-36994-w

MX Unit Website

For further information please visit the MX Unit Website

Genómica Estrutural (PT)

Unidade de Cristalografia de Macromoléculas

O laboratório de Genómica Estrutural tem como objectivo o estudo de proteínas envolvidas em diversos processos biológicos, nomeadamente na reparação e proteção do DNA, resistência ao stress oxidativo, e metabolismo do sulfureto de hidrogénio, através de uma abordagem de genómica estrutural. As proteínas de interesses provêm de organismos procariotas e eucariotas (unicellulares e humanos). O laboratório emprega uma abordagem multidisciplinar em que se combinam métodos de biologia estrutural como a cristalografia de raios-X e small-angle X-ray scattering, com X-ray imaging, métodos bioquímicos, biofísicos e espectroscópicos. A nossa estratégia de investigação tem como objectivo uma compreensão detalhada da fisiologia microbiana e humana, combinada com potenciais aplicações biotecnológicas e farmacêuticas das proteínas em estudo. O Laboratório compreende três grupos de investigação integrados nas Unidades MOSTMICRO e iNOVA4Health do ITQB NOVA.

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