Metabolic engineering with multi-objective optimization of kinetic models

Kinetic models have a great potential for metabolic engineering applications. They can be used for testing which genetic and regulatory modifications can increase the production of metabolites of interest, while simultaneously monitoring other key functions of the host organism. This work presents a methodology for increasing productivity in biotechnological processes exploiting dynamic models. It uses multi-objective dynamic optimization to identify the combination of targets (enzymatic modifications) and the degree of up- or down-regulation that must be performed in order to optimize a set of pre-defined performance metrics subject to process constraints. The capabilities of the approach are demonstrated on a realistic and computationally challenging application: a large-scale metabolic model of Chinese Hamster Ovary cells (CHO), which are used for antibody production in a fed-batch process. The proposed methodology manages to provide a sustained and robust growth in CHO cells, increasing productivity while simultaneously increasing biomass production, product titer, and keeping the concentrations of lactate and ammonia at low values. The approach presented here can be used for optimizing metabolic models by finding the best combination of targets and their optimal level of up/down-regulation. Furthermore, it can accommodate additional trade-offs and constraints with great flexibility.

Behavior-based price discrimination in a multi-dimensional preferences market

NIPE WP 04/ 2016

Development of a novel aptamer-based multi-sensor device for the detection of osteopontin

Doctoral Dissertation for PhD degree in Chemical and Biological Engineering

Da metrópole ao enclave e vice-versa. A ideia de cultura num agente destacado do enclave galego de Lisboa: Alfredo Guisado

O enclave galego de Lisboa, escassamente estudado se comparado com os enclaves americanos, experimentou importantes mudanças de variado tipo entre finais do século XIX e primeiras décadas do seguinte. Seguindo o percurso de Alfredo Guisado (1891 -1975), proponho aqui algumas hipóteses acerca das relações que se estabeleceram entre o enclave e a metrópole, e dentro daquele, no plano cultural.

Experimental procedures for the identification of material properties of intervertebal disc - a contribution for the development of biomimetic substitutes for the nucleus pulposus

Tese de Doutoramento em Engenharia Mecânica.

Optimização do processo de recolha de resíduos: desenvolvimento de ferramentas de investigação operacional para o problema de orientação de equipas com multi-restrições

Tese de Doutoramento em Engenharia Industrial e de Sistemas.