Proteomics of Chronic Lung Diseases (Cystic Fibrosis, Asthma, COPD):
Leading to Biomarkers and Therapeutic Target Discovery

Study of the human ß-globin mRNA

Determination of Dental Caries Associated Factors

Comprehensive Proteomic Analysis of TTR induced Proteins in hepatomas

Proteomics of Chronic Lung Diseases (Cystic Fibrosis, Asthma, COPD):
Leading to Biomarkers and Therapeutic Target Discovery

Cystic fibrosis (CF) lung disease, characterized by chronic lung infection and inflammation, remains the most life-threatening clinical feature in CF accounting for 95% of morbidity and mortality. Despite enormous progress in our knowledge of the genetic and molecular basis of CF, there is no effective therapy available for the disease.
There are several pulmonary disorders that share some features with CF. Chronic obstructive pulmonary disease (COPD) and asthma are two examples of these pulmonary disorders with a high incidence worldwide. COPD is characterized by a chronic airway limitation to airflow, due to bronchitis or emphysema. Chronic inflammation and remodelling are characteristic features of the conducting airways in asthma. Possible influences of CFTR gene mutations in COPD and asthma phenotype have been reported. Therefore, it is attractive to consider COPD and asthma together with CF in a comparative study.

Therefore, by carrying out an unique proteomic comparative study in patients with CF and other chronic lung diseases, such as chronic obstructive pulmonary disease (COPD) and asthma, the main purpose of this project is the identification of proteins differentially expressed in human native CF cells and tissues as specific biomarkers that may be useful as diagnostic/prognostic indicators of CF lung disease. Biomarkers associated with COPD and asthma are also likely to be revealed. Nasal airway cells and blood from patients and healthy controls will be investigated by conventional genomics and innovative proteomics-based approaches.

Project Responsible

Deborah Penque, PhD, Laboratório de Proteómica, Centro de Genética Humana do INSA- FCT/ POCTI/SAU-MMO/56163/2004

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Study of the human ß-globin mRNA nonsense-mediated decay mechanism

Accurate gene function depends on a low error rate of each step of the gene expression pathway. The fidelity of gene expression is enhanced further by a quality control mechanism against faulty mRNAs with premature translation termination codons, which has been termed nonsense-mediated mRNA decay (NMD). After the phenomenon of NMD was first described in a patient with ß-thalassemia, the human ß-globin gene has been central in elucidating the mechanism.

The objective of our project is to investigate specific factors involved in targeting a nonsense-mutated human ß-globin mRNA for decay, by functional proteomics. By using two-dimensional polyacrylamide gel electrophoresis, we intend to identify and characterize proteins specifically and differentially expressed in cell lines stably transfected with a normal or a nonsense-mutated human ß-globin gene.

Project Responsible

Luisa Romão, PhD: Assistant Researcher, Centro de Genética Humana, Instituto Instituto Nacional de Saúde Dr. Ricardo Jorge (Lisboa).

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Determination of Dental Caries Associated Factors Using Proteomics Methodologies

Objectives:
- to determine saliva protein patterns associated with dental caries using proteomics
- to establish new therapeutic strategies to dental caries.

Dental caries is a multifactorial chronic disease that involves the destruction of tooth structure, which can lead to loss of masticatory function and unesthetic appearance of affected teeth. More than 80% of mankind suffers dental caries disease. Among the host factors that affect dental caries, perhaps the most obvious is saliva, with an important role in the maintenance of health of both soft and hard oral tissues.
The aim of this study is to investigate saliva protein profiles and their probable association with caries activity. Two groups of subjects have been selected by their caries status: caries free, and caries active and the 1D and 2D SDS-PAGE electropherograms compared and proteins identified by mass spectrometry.

Project Responsibles

Francisco Amado, PhD: Assistant Professor, Departamento de Química, Universidade de Aveiro.
Pedro Domingues, PhD: Assistant Professor, Departamento de Química, Universidade de Aveiro

Comprehensive Proteomic Analysis of TTR induced Proteins in hepatomas

Familial Amyloidotic Polyneuropathy (FAP) is characterized by deposits of insoluble amyloid fibres in which transthyretin (TTR) is the major protein component. TTR is a tetramer with identical 127 aminoacid sub-units and an extensive ß-sheet structure. More than 80 TTR mutations have been associated with autosomal dominant amyloidosis, usually presenting with peripheral and autonomic neuropathy and/or cardiomyopathy.
With this study we aim to identify and characterise novel proteins implicated in the metabolism of TTR.
A comparative 2D analysis methodology is being used to identify proteins that are differentially expressed in hepatomas in the presence and absence of TTR.

Project Responsible

Maria João Saraiva, PhD, Departamento de Neurobiologia Molecular, IBMC, Porto.

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