Research

THEMATIC AREAS | RESEARCH THRUST AREAS

IBB activities are focused in four thematic areas:

Industrial Biotechnology

Health Biotechnology

Agricultural Biotechnology

Environmental Biotechnology and Chemistry

INDUSTRIAL BIOTECHNOLOGY

Industrial biotechnology concerns the application of modern biotechnology for the industrial production of added-value chemical substances and bio-energy, using inherently clean processes, with waste minimisation and reduced energy consumption. Multidisciplinary activities are pursuit in which biochemistry, microbiology, molecular and cell biology, genomics and bioinformatics and process engineering are integrated and combined aiming the development of useful processes and products based on microbial, animal or plant cells, their organelles or enzymes as biocatalysts.

The Laboratorio Associado IBB is committed to develop R&D activities within the thematic area of Industrial Biotechnology on three major topics:

A) Biological and Chemical Processes – Molecular and Cell Engineering; Reaction Engineering; Purification of Biomolecules and Valorisation of Natural Products; and Process design.

B) Nanobiotechnology – Micro- and Nano-devices; Nano-structured catalytic materials; and Nanoparticles

C) Modelling of Biological and Chemical Systems - Computational and predictive models; and Biosystems analysis

HEALTH BIOTECHNOLOGY

Biological and biomedical research is in the midst of a transition period, experiencing significant developments driven by the massive increase of genomic and proteomic information in public databases, and by the technological developments to exploit such information (i.e. DNA chips, gene targeting, stem cell technology). The cross-disciplinary expertise gathered by IBB members enables the integration of knowledge from molecular, structural and cell biology, biochemistry, biotechnology, genomics and bioinformatics, gene targeting, cell and tissue engineering.

Within the thematic area of Health Biotechnology, the Laboratorio Associado IBB is committed to develop R&D activities specifically on four major aspects:

A) Molecular Determinants and Mechanisms of Disease – Drug resistance and Microbial pathogenesis and epidemiology; Polymorphism screening and cancer susceptibility; Cancer molecular cyto/genetics; Protein function, structure, activity and their implication in disease onset; and Genetic control of organogenesis.

B) Diagnostic Tools - Generic biochip and biosensors platforms; and Comparative genomics, transcriptomics and proteomics techniques for gene expression identification and diagnostics.

C) Molecular Therapeutic Technologies -Vectors for gene therapy and vaccination; and Controlled/sustained drug delivery and targeting.

D) Stem Cells, Biomaterials and Tissue Engineering – Stem Cell and Tissue Engineering; Novel biomaterials and biomaterials modification, bioactivity and biomimetic coatings.

 

AGRICULTURAL BIOTECHNOLOGY

The thematic area of Agriculture Biotechnology focuses on the application of expertises in functional, comparative and evolution genomics, molecular genetics, to biological systems of interest in agriculture, animal biotechnology and food processing.

The Laboratorio Associado IBB is committed to develop R&D activities within the thematic area of Agricultural Biotechnology on five major topics:

A) Genetic Variability - Natural and induced (mutagenesis) genetic variability in plants, animals and microorganisms.

B) Plant and Animal Functional, Comparative and Evolution Genomics - Comparative and evolution genomics of crop and forestry species and mammalian species; Molecular cytogenetics; and Genome organisation in plants and animals.

C) Genetic Resources and Plant breeding - Genetic resources preservation strategies and plant breeding

D) Plant and Animal Biotechnology - In vitro culture and micropropagation; Selection of DNA markers in animals and plants; Proteomics of metal ions stress in plants; Somatropic genes variants and alternative transcripts in sheep; and Food traceability.

E) Microbiology and Wine Technology - Identification, physiology, metabolism and genomic, transcriptomic and metabolomic characterisation of wine microorganisms.

ENVIRONMENTAL BIOTECHNOLOGY AND CHEMISTRY

The main objective of this area is to respond to industrial and society demand for efficient environmental protection technologies through the combination of process development and fundamental research on the biological and chemical phenomena supporting the currently implemented industrial processes. The development of innovative technologies for industrial pollution prevention, control and monitoring, and for industrial wastewater treatment, and identification of the biological effects of exposure to polluting agents are pursuit.

 

The Laboratorio Associado IBB is committed to develop R&D activities within the thematic area of Environmental Biotechnology and Chemistry on four major topics:

A) Integrated Pollution Prevention and Control - Integrated approaches for waste and/or effluent minimisation; and Implementation of expert systems.

B) Treatment Processes and Technologies – Analysis of natural and artificial ecosystems; and Novel treatment technologies of highly toxic substances.

C) Bio/catalytic Materials and Processes for Gas-phase Effluent Treatment – VOC reduction; and NOx and SOx elimination.

D) Non-Conventional Biological Diagnostic and Monitoring Systems – Image analysis; Biological models; and Environmental biosensors.

 

RESEARCH THRUST AREAS

The members of IBB have developed expertises and competences in six thrust areas:

1. Biomolecular Science and Engineering;

2. Genetics Molecular and Cell Biology;

3. Functional Comparative and Evolution Genomics;

4. Bioprocess and Biosystems Engineering;

5. Biomaterials for Tissue Engineering and Regenerative Medicine;

6. Catalysis and Reaction Engineering.

Biomolecular Science and Engineering

Biomolecular Science and Engineering thrust area aims at studying the structure/function and molecular recognition of biological molecules (proteins and nucleic acids) and structures (membranes, virus, proteasome) and their applications in the industrial and health sectors. IBB research units have developed expertises on: Protein and Enzyme Engineering, Nucleic Acid Engineering and Nanobiotechnology.

Protein and Enzyme Engineering is focused on the design of functionally active and stable proteins, namely enzymes and therapeutic proteins, using in silico structure analysis and modelling, recombinant DNA technology, directed evolution, protein immobilisation, spectroscopic techniques and medium engineering. The assessment of structural stability, folding/unfolding pathways and protein-protein interactions can provide insight on the mechanisms underlying the formation of protein deposits occurring in amyloid and prion diseases. Mechanisms of protein assembly are also essential to build protein complexes such as the proteasome, chaperones, oligomeric enzymes, and virus-like nanoparticles.

Nucleic Acid Engineering is focused on DNA-based technology for gene therapy, diagnostics and vaccination. Particular attention is given to the design of plasmid vectors and selected hosts as well as to structural and stability studies of plasmid DNA to facilitate purification and enhance biological activity.

Nanobiotechnology, integrates nano/microfabrication and biosystems and generates powerful methods that allow substantial new insights into biological systems function. Microelectronically based chips are developed to design and assemble devices for genetic analysis. Screening and identification of single nucleotide polymorphisms (SNPs) and gene expression patterns are performed by hybridising appropriate biological samples on microarray devices (DNA chips). Charge transfer through DNA is used for the direct transduction of DNA hybridisation on gold microelectrodes and for the simultaneous detection of DNA polymorphisms by electrochemical methods. Piezoelectric and optical transduction based on energy transfer and fluorescent quenching using semiconductor nanocrystals are also investigated. The effects of nano (and micro) patterning on cell adhesion and differentiation are also assessed.

Genetics, Molecular and Cell Biology

The Genetics, Molecular and Cell Biology thrust area aims at developing research programmes in the domains of Life, Biomedical and Agricultural Sciences at the cellular and molecular levels.

IBB research activities focus on the molecular mechanisms of response of cells to chemicals (drug/xenobiotic/endobiotic) or other stress stimuli. In this context, yeast cells, human cell lines, primary animal cell cultures, knocked-out mice and other animal models, are used to identify and elucidate the role of multidrug resistance (MDR) and ABC transporters, as well as drug metabolising enzymes (DME) in the cell response to stress and in the mechanism of acquired resistance.

Pharmacogenetics, gene expression approaches, DNA pooling strategies, and multiplex amplification and genotyping methodologies, are used to evaluate the effect of inter-individual genomic variability in determining the individual outcome of therapeutics as well as in epidemiological studies. Of particular interest is the evaluation of the association and role of polymorphic genes involved in the metabolic fate of xenobiotics, DNA repair, and in the control of cell cycle in oncological, cardiovascular, and infectious diseases. Large epidemiological surveys are also realized in different disease settings in particular focusing bacteria belonging to the Burkholdera cepacia complex (Bcc) and human DMEs in cystic fibrosis and malaria infection, respectively.

Polymorphism analysis is also used to study genetic variability in plants, animals and microorganisms. Particular focus is given to crop species, fruit trees and forestry species, in bovidae and suinae species; and to the identification and strain differentiation of Lactic Acid Bacteria and Saccharomyces cerevisiae in fermentation and wine production.

 

Functional, Comparative and Evolution Genomics

The Functional, Comparative and Evolution Genomics thrust area aims at developing integrated and cross disciplinary research programmes in the domain of Life, Biomedical and Agricultural Sciences by applying the experimental and computational approaches of the post-genomic era.

 

Combined approaches taking full advantage of the potentialities of Saccharomyces cerevisiae, chick embryos, mouse transgenics, embryonic stem cells, and other cellular or animal models, of gene targeting, identification, manipulation, and analysis technologies (i.e. siRNA and GeneChip technologies), and of bioinformatic tools are used to investigate signaling pathways, gene regulation, expression, and function and transcriptome analysis. Such approaches are used in topics of biomedical relevance such as brain development and vertebrate hemangioblast/cardiogenesis, and to elucidate the regulatory networks underlying yeast responses to a number of chemical stresses of interest in Food and Biotechnological Industries, in Agriculture, and in Medicine. Similarly, systems biology approaches, involving the combination of in silico, comparativefunctional genomics and proteomics, are applied to other microorganisms, mainly Pseudomonas related bacteria and pathogenic yeast species Candida albicans and Candida glabrata.

Comparative Genomics of forest and crop species is performed using heterologous probes such as genomic DNA from wild relatives, repetitive DNA sequences and transgenes in order to evaluate the rearrangements of the genomes of closely related species and infer the results under an evolution point of view. Molecular Cytogenetic approaches are applied to analyse pre-meiotic and meiotic events in developing wheat, rye and barley anthers, and to investigate the organisation of transgenes delivered into wheat, tritordeum, Vitis and other genomes.

Bioprocess and Biosystems Engineering

 

The goals of this research thrust area are to establish and model engineering strategies in order to establish improved biological and chemical processes.

Bioprocess engineering is focused on the development of processes, based on microbial and animal cells, to produce engineered biomolecules and valuable metabolites. Bioconversion processes in conventional and non-conventional media are carried out in selected type of bioreactors. Bioreactor characterisation and design include microbioreactors, multiphase bioreactors, biofilm reactors, oscillatory flow reactors, hyperbaric bioreactors and cell culture reactors for the production of cells and bioactive molecules, as well as for food and environmental applications.

 

Process development for production and purification of antibodies, growth factors, proteins, nucleic acids, and nanoparticles and nano-structures for drug delivery are performed, matching the growing industrial need for biopharmaceutical and nanobiotechnology applications. Novel bioseparation methods are established aiming high product purity, process consistency and economy.

 

Stem Cell Bioengineering research is focused on the development of bioreactor culture systems for human hematopoietic stem/progenitor cells (HSC), human mesenchymal stem cells (MSC) and mouse embryonic stem cells (ESC) in an ex-vivo environment. The molecular and cellular mechanisms involved in expansion and differentiation, the kinetics of the ex-vivo stem cell expansion/maintenance and differentiation are addressed. Predictive kinetic models are used to describe stem cell fate. Priority is also given to novel concepts and devices for stem cell isolation and differentiation.

Biosystems Engineering explores the development of Systems Engineering to bioprocess monitoring and control and the integrative mathematic and chemometric approaches for elucidation and analysis of biosystems. Advanced process monitoring and control and novel sensor technology, such as intelligent real-time control systems with on-line learning capabilities, are studied within the framework of process analytical technologies (PAT) applied to biological and pharmaceutical engineering production.

 

Biomaterials for Tissue Engineering and Regenerative Medicine

 

Biomaterials research is focused on the development, optimisation and characterisation of novel materials derived from biocompatible natural polymers. Materials with high versatility in terms of chemical and physical properties are generated for different applications in the fields of nanocomposites, stem cell growth and differentiation, tissue engineering and regenerative medicine.

 

Biomaterial surface modification is performed to manipulate and optimize key surface parameters for cell adhesion and proliferation as well as for biomolecule immobilisation in different tissue engineering applications, micro and nano biological sensors, and enzyme immobilisation.

 

Functional tissue engineering hybrid constructs, combining human mesenchymal stem cells (MSC) technology and materials science are developed aiming at bone and cartilage replacement/regeneration. Biomaterial scaffolds are seeded in vitro with human microvascular endothelial cells to evaluate endothelial cell attachment and anginogenesis.

 

Catalysis and Reaction Engineering

 

The goal of this area is to integrate and develop knowledge on reaction engineering, namely on what concerns catalytic processes.

 

Molecular and kinetic modelling techniques are applied to understand and improve existing chemical processes as well as to complex systems, namely biological systems, such as enzyme catalysis and animal cell expansion and differentiation.

 

Catalysts, either zeolite or non-zeolite based, are developed for industrial applications, for catalytic transformation of hydrocarbons for the petroleum and petrochemical industries. Nano-structured materials are also designed aiming environmental applications in particular for pollutant reduction including VOC and NOx elimination.

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