Theme Leader: Nuno Pereira Mira

The application of intensive metabolic engineering approaches, often based on gene- and/or genome- editing, has opened the doors to the development of “new-to-nature” microbial catalysts that can be explored as cellular factories for the production of add-value compounds. Our work has been focusing the exploration of various Yeast species, with a particular emphasis on Saccharomyces cerevisae, as potential hosts to be used in industrial biotechnology for the production of add-value chemicals including wine and building block molecules like organic acids or relevant derivatives. For the design (or re-design) of these more robust yeast strains information obtained at various genomic levels is being obtained further complemented by computational metabolic modeling.

Our current topics in this field include:

  • Pathway prospecting to implement new-to-nature biochemical pathways for the production of organic acids and relevant derivatives
  • Fostering the utilization of Yeasts (Saccharomyces cerevisiae and other Non-Saccharomyces species) as microbial cell factories by exploring insights gathered from the biology and physiology of these species
  • Implementation and development of computational metabolic modeling approaches to boost the engineering of more robust microbial catalysts
  • Engineering of mixed starter cultures composed of S. cerevisiae and non-Saccharomyces species to boost biotechnological applications

Publications

  1. Seixas I, Barbosa C, Mendes-Faia A, Güldener U, Tenreiro R, Mendes-Ferreira A*and Mira NP*, Genome sequence of the non-conventional wine yeast Hanseniaspora guilliermondiiUTAD222 unveils relevant traits of this species and of the Hanseniasporagenus in the context of wine fermentation, DNA Research, (2018)(in press)
  2. Tavares MJ, Ulrich G, Esteves M, Mendes-Faia A, Mendes-Ferreira A and Mira NP, “Genome sequence of the wine yeast Saccharomycodes ludwigiiUTAD17”, Genome Announcements,(2018) (in press)
  3. Seixas I, Barbosa C, Salazar SB, Mendes-Faia A, Wang Y, Guldener U, Mendes-Ferreira Ana and Mira NP, Genome sequence of the non-conventional yeast Hanseniaspora guilliermondiiUTAD222, Genome Announcements,5(5)e01515-16(2017)

  4. Barbosa C, Faia A, Lage P, Mira NPand Mendes-Ferreira A,Genomic expression program of Saccharomyces cerevisiaealong a mixed-culture wine fermentation with Hanseniaspora guilliermondii, Microbial Cell Factories, 14:124, (2015)

 

External collaborators

  1. Alexandra Mendes-Ferreira, Universidade de Trás-os-Montes e Alto Douro, Portugal
  2. Susana Vinga, IDMEC-Center of Intelligent Systems, Portugal
  3. Kristala Prather, MIT, United States
  4. Marie-France Sagot, INRIA, France
  5. Zengyi Shao, Iowa State University, United States
  6. Laura Jarboe, Iowa State University, United States

Funded research projects

  1. TTRAFIC – Toxicity and TRAnsport for Fungal production of Industrial Compounds – EraNet in Industrial Biotechnology – 6th call (March 2016-March 2019) (ERA-IB-2-6/0003/2014)
  2. SMARTWINE – Smarter wine fermentations: integrating Omic-tools for the development of novel mixed-starter cultures for tailored-made wine production (PTDC/AGR-TEC/3315/2014) (1/11/2015-1/11/2018)
  3. IST-NFS interaction Grant: Towards the development of sustainable bioprocesses for microbial production of carboxylic acids using renewable raw materials, awarded by Fundação Luso-Americana para o Desenvolvimento
  4. ITACYEAST – Exploring a molecular systems biology approach to implement yeast-based processes for production of itaconic acid from renewable carbon sources, Internal projects awarded by the Institute for Bioengineering and Biosciences (1/7/2015-1/7/2016)
  5. LEVITA – Towards sustainable microbial production of itaconic and levulinic acids, Twinning program of the EraSynBio research program (April 2014-October 2014)

Other research lines

Another topic that we have been working on concerns the study of molecular mechanisms underlying the high competitiveness of pathogenic Candida species (in particular, C. albicans and C. glabrata) in infection sites. In specific we have been working on the characterization of the molecular responses of Candida spp. to environmental stresses relevant in the context of the infection including the presence of a commensal microbiota or of antifungal drugs, among others. We have also been working on the identification of new molecules that could be used as anti-Candida agents either free, used in combination with currently used antifungals or used to tailor biomedical materials frequently colonized by pathogenic yeasts. On the overall it is expected that the knowledge generated could foster the development of novel therapeutic strategies, focused on non-conventional targets, for the treatment of candidiasis, widely recognized as an emergent disease.

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Our current topics in this field include:

  • Study the molecular mechanisms underlying the responses of C. albicans and C. glabrata to commensal bacteria or to toxic molecules produced by these bacteria such as carboxylic acids;
  • Foster the exploitation of Ag- and Zn- based compounds as anti-Candida molecules
  • Explore comparative genomics to unravel new mechanisms of antifungal resistance and adaptation to the human host in Candida spp

Publications

 

  1. Marques L, Alves MM, Eugénio S, Salazar SB, Pedro N, Grenho L, Mira NP, Fernandes MH and Montemor MF, Potential anti-cancer and anti-Candidaactivity of Zn-derived foams, Journal of Materials Chemistry B, 6, 2821-2830, (2018)
  2. Alves MM, Marques LM, Nogueira I, Santos CF, Salazar SB, Eugénio S, Mira NP and Montemor F, In silico, in vitro and antifungal activity of the surface layers formed on zinc upon this biomaterial degradation, Applied Surface Science, (2018)(in press)
  3. Cavalheiro M, Costa C, Silva-Dias A, Miranda IM, Wang C, Pais P, Pinto SN, Mil-Homens D, Sato-Okamoto M, Takahashi-Nakaguchi A, Silva RM, Mira NP, Fialho AM, Chibana H, Rodriges AG, Butler G and Teixeira MC, Unveiling the mechanisms of in vitro evolution towards fluconazole resistance of a Candida glabrataclinical isolate: a transcriptomics approach, Antimicrobials Agents and Chemotherapy, (2018) (in press)
  4. Alves MM, Cunha DV, Santos CF, Mira NP and Montemor F, Microstructured ZnO-rod like coating prevents biofilm formation prompted by pathogenic Candida spp, Ceramics International, 44(4), 4467-4472, 2018
  5. Salazar SB, Wang C, Munsterkotter M, Okamoto M, Takahashi-Nakaguchi A, Chibana H, Lopes MM, Guldener U, Butler G and Mira NP, Comparative genomic and transcriptomic analyses unveil novel features of azole resistance and adaptation to the human host in Candida glabrataFEMS Yeast Res, 18(1), (2018)
  6. Bernardo R, Cunha DV, Wang C, Pereira L, Silva S, Salazar SB, Schroeder MS, Okamoto M, Takahashi-Nakaguchi A, Chibana H, Aoyoama T, Sá-Correia I, Azeredo J, Butler G and Mira NP, The CgHaa1-regulon mediates response and tolerance to acetic acid stress in the human pathogen Candida glabrata, G3: Genes, Genomes and Genetics, 7: 1-18, (2017)

External collaborators

  1. Geraldine Butler, University College Dublin, Ireland
  2. Hiroji Chibana, Chiba University, Japan
  3. Marta Alves, CQE-Instituto Superior Técnico, Portugal
  4. Ulrich Guldener, Technical University Munich
  5. Fernanda Carvalho, CQE-Instituto Superior Técnico, Portugal
  6. Alberto Delbem e Débora B Barbosa, Universidade Estadual de São Paulo, Brasil
  7. Sara C Madeira, Faculdade Ciências da Universidade de Lisboa, Portugal

Funded research projects

  1. LactoCan (1/10/2018-31/12/2009) – Exploring the interference between Candida spp. and lactobacilii to foster the development of non-conventional antifungal therapies (PTDC/BIA-MIC/31515/2017)
  2. PANCANDIDA (1/1/2014 –1/1/2016) – Towards the development of novel diagnosis tools for the early detection of invasive infections caused by C. albicans and C. glabrata, funded by Gilead Pharmaceuticals within the scope of the Gilead Génese Program
  3. Pfizer agreement: WI178570, “Unravelling the molecular mechanisms of acquired antifungal resistance in Candida glabrata: a genomics approach”