The following research thrust areas have been identified for collaborative Portuguese and MIT faculty and doctoral student research projects:

Research Thrust Area: Bioprocess and Biomolecular Engineering

This thrust area is focused on the affinity purification of monoclonal antibodies, the use of micro-bioreactors to produce recombinant proteins by mammalian cells and the upstream and downstream processing challenges associated with large scale production of plasmid vectors using high-density cell cultures.

Research Projects:

Protein Purification using Magnetic Particles

The overall goal of this project is to develop magnetic nanoparticles from a promising technology to an industrially relevant separation. The emphasis on the use of the magnetic nanoparticles will address the purification of monoclonal antibodies from animal cell culture broths.

Faculty: Daniel Wang (MIT), Ana Cecilia Roque (FCT – UNL)


Rational engineering of E. coli strains and vectors for improved manufacturing of plasmid biopharmaceuticals

The overall goal of this project is to develop and test an E. coli strain specifically adapted to meet the upstream and downstream processing challenges associated with large scale production of plasmid vectors. By rationally engineering specific genes we aim to deliver a host capable of striving in high-density cell cultures while synthesizing large amounts of supercoiled plasmids at a high plasmid/impurity ratio

Faculty: Kristala Prather Jones (MIT), Miguel Prazeres and Gabriel Monteiro (IST)


High Through-Put Screening with Microbioreactors

The overall goal of this project is to use micro-bioreactors to rapidly screen for mammalian cell clones which have capabilities to over-express the proteins. This will be achieved using a high through-put mode to reduce time and labor for finding the best clone(s) with the capabilities of producing high product concentrations.

Faculty: Daniel Wang (MIT), Manuel Carrondo and Paula Alves (ITQB/IBET)


Yeast Surface Display of Protein A Mimics

The main goal of this project is to develop single fibronectin Ig domains with binding affinity mimicking that of Protein A by a yeast-surface display combinatorial approach. The particular aim is to develop new purification methodologies, with emphasis on milder elution conditions to avoid antibody aggregation. The stability and binding properties of the Protein A mimics will be engineered by both directed evolution and rational design.

Faculty: K. Dane Wittrup (MIT), Angela Taipa (IST)

Research Thrust Area: Cell and Tissue Engineering

The thrust area aims at the ex-vivo expansion of stem cells and their highly controlled differentiation into specific cell types and 3D cell culture for cell therapy and drug screening.  This thrust area also aims to develop innovative and smart scaffold materials and study the performance of tissue-like substitutes obtained by in vitro culturing stem cells obtained from different sources onto these scaffolds in different culturing conditions. Human hematopoietic stem cells, mesenchymal stem cells, embryonic stem cells, primary liver cells, cancerous cells and mouse embryonic and neural stem cells are used as model systems.

Research Projects:

Three-dimensional Culture: another dimension for the ex-vivo expansion and neural differentiation of embryonic stem cells

This project addresses the expansion of both embryonic stem cells (ESC) and neural stem cells (NSC) bioreactor systems. Biocompatible materials (hydrogels based on collagen, hyaluronic acid or dextran), largely used in regenerative medicine and tissue engineering, will be screened using a microscale platform for the in vitro expansion and neural differentiation of both ESC and NSC. The main goal is to design hydrogel scaffolds able to recreate the in vivo 3-D cellular environment that supports stem cell viability and differentiation. The expansion and differentiation status of encapsulated stem cells will be further evaluated by high-throughput gene analysis.

Faculty: Robert Langer (MIT), Claudia Lobato da Silva, Joaquim Cabral (IST) and Lino Ferreira (CNC-Coimbra)


Depicting the Bone Marrow Microenvironment towards the ex-vivo Expansion of Hematopoietic Stem Cells

This project aims to contribute for a better knowledge from the hematopoietic niche towards the development of novel strategies for the ex-vivo expansion of human hematopoietic stem/progenitor cells (HSPC) for use in multiple settings such as cell therapy (e.g. BM transplantation) or gene therapy. The major breakthroughs of this project are expected to boost ex-vivo expansion technologies, by contributing for the development of new methods to promote HSPC expansion without differentiation.

Faculty: Sangeeta Bhatia (MIT), Claudia Lobato da Silva and Joaquim Cabral (IST)


Bioactive Beads for Local Modulation and Sensing of Cell Mechanical Environment in 3D Engineered Tissues

In this project, cell-sized hydrogel microbeads with defined and systematically varied mechanical properties and with cell-interactive surface properties, will be developed with the aim of incorporating the beads into 3D tissue models so that the beads both provide local modulation of cell behavior as well as recording key aspects of cell behavior via special reactive moieties buried within the surface coating.

Faculty: Paula Hammond and Linda Griffith (MIT), Ana Ricardo (FCT-UNL)


Research Thrust Area: Computational Bioengineering, Genomics, Systems and Synthetic Biology

This thrust area is focused on: (i) Application of optimal experimental design techniques in the context of System Biology; (ii) Synthetic Biology by the design of bacteria to produce therapeutic agents and the use of life bacteria as targeted delivery systems; and (iii) Toxicogenomics to elucidate gene-environment interactions and favors the establishment of parallelisms between different organisms with impact in Environmental Safety and Human Health, Agriculture and Biotechnology.

Research Project:

Application of Optimal Experimental Design in the Context of Systems Biology

Systems biology is expected to bring major benefits to industrial biotechnology especially in the development of efficient cell factories, by speeding up the development process, and ensuring that new products can be brought to the market faster or that there can be a faster improvement of existing bioprocesses. Therefore, the ultimate aims of this project are associated with aiding efforts to the optimization of industrial biotechnology processes like the production of bulk chemicals (e.g. succinate or lactate), biofuels (e.g.bioethanol) and specialty chemicals (e.g. vitamins and antibiotics). A set of mathematical and computational techniques will be developed and applied to the problem of designing efficient and informative experiments for the identification of kinetic models representing metabolic reactions.

Faculty: Bruce Tidor (MIT), Eugenio Ferreira and Isabel Rocha (U. Minho)

Research Thrust Area: Biomedical Devices and Technologies - Hybrid Human-Machine Systems

This Hybrid Human-Machine research effort is motivated by a desire to better quantify and model human and human-machine performance. We hope to contribute knowledge and mechanical designs that might aid individuals with mobility and musculoskeletal disabilities. Biomedical devices, such as powered ankle-foot prostheses, musculoskeletal loading suits and exoskeletons, and wearable brain sensors hold promise for medical applications. Several challenges exist on the design side, including human factors, power sources, actuation, and controllers. On one hand, there are purely mechanical and electrical challenges, but on the other hand, we must also understand the biology and intent of movement to most effectively design these biomedical devices. Our hybrid human-machine system research attempts to augment human capability, alleviate mobility disability in locomotion, understand control strategies used by people when augmented by exoskeletons, and incorporate wearable sensors and electronic textiles.

Research Project:

Locomotion, Powered Prosthesis, and Exoskeleton Suit Development

This Hybrid Human-Machine research effort is motivated by a desire to better quantify and model human and human-machine performance. We hope to contribute knowledge and mechanical designs that might aid individuals with mobility and musculoskeletal disabilities. Our hybrid human-machine system research attempts to augment human capability, alleviate mobility disability in locomotion, understand control strategies used by people when augmented by exoskeletons, and incorporate wearable sensors and electronic textiles.

Faculty: Dava Newman and Hugh Herr (MIT), Estela Bicho (U Minho), Jorge Martins and Miguel Silva (IST)

Read about the January 2010 edition of the Biomedical Devices and Technologies module at IST that was open to non-MPP researchers and received 30 additional participants, who engaged in dialogue with industry leaders in this domain.


Research Thrust Area: Biosystems Innovation, Management and Policy

Biotechnology/Bioengineering as a business was born around 1976 with the creation of Genentech. This company set an example for turning science into a profitable business that has inspired numerous other ventures. However, in spite of the growth in revenues of the industry as a whole, success has remained elusive for most biotech firms which typically earn no profit. Understanding the key drivers behind the success of ventures is critical to increase the rate of success of biotech ventures. Innovation has important implications for the competitive advantage of biotech and bioengineering companies, and also for those countries which have targeted the sector as a priority. It is a key element of great significance in the reduction of the much feared technological challenges. The goal of this thrust area is to investigate and promote innovation, management and policy in Biotechnology/Bioengineering at the world wide scale, while simultaneously addressing and probing it the specificities of the sector in Portugal.

Research Project:

Determinants and Measurements of Innovation in Bioengineering: A Cross-National Study of Successful and Unsuccessful Cases

Innovation is recognized as a key driver to create economic wealth in modern economies. The role of innovation is particularly critical in sectors like bioengineering, with an increasing demand to translate technological advances into competitive advantages. This project is aimed to address the shortage of measurement tools to assess innovation in bioengineering by creating, among others an innovation scorecard and a web-based tool which will serve as a repository of the data collected during the course of the project, while simultaneously allowing the data to be retrieve and displayed according to the metrics developed.

Faculty: Charles Cooney, Ken Zolot (MIT), Luis Lage (FE –UNL, Isabel Rocha (U Minho), Miguel Prazeres (IST) and Pedro Saraiva (U Coimbra)