Manuel J.T. Carrondo Lab
Animal Cell Technology Unit
Our research is centered on integrative development of bioprocesses for complex biopharmaceuticals namely vaccines, recombinant proteins, viral vectors for gene therapy and cells/stem cells for cell therapy applications. |
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Manuel J.T. Carrondo PhD in 1979, Environmental Engineering, Imperial College, London Phone (+351) 214469469 | Extension 1469 |
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Research Interests
Within the Animal Cell Technology Unit (ACTU), the Engineering Cellular Applications Laboratory integrates upstream and downstream processes with physico – mathematical tools towards the development of bioprocesses for complex and novel biopharmaceuticals. Simplicity, feasibility, transferability and economics are criteria used to design processes that may find industrialization opportunities. Having started with post-translational modified protein biopharmaceuticals in the early 90s, such criteria, design and process applications have been extended to vaccines (e.g. multivalent Influenza VLPs, retro-VLPs, HIG Gag-VLPs, ZIKV-VLPs, viral vaccines…) and viral vectors for gene therapy (e.g. adenoviruses, retroviruses, lentiviruses, AAVs,…), drawing from the expertise and research achievements of the other labs in the ACTU. In the Engineering Cellular Applications Laboratory, bioprocess development comprises the optimization of mammalian and insect cells expression systems (stable or transient expression), evaluation of different bioreactor operation modes (e.g. fed-batch and perfusion), application of scale-down models for high-throughput screening, design of novel continuous purification processes, modelling towards biological and chemical process control, and scale-up for pre-clinical applications. More recently, metabolic systems biology (e.g. 13C tracer experiments for fluxome estimation and exometabolome profiling by 1H-NMR) has been assisting bioprocess development in areas such as cancer cell metabolism (e.g. lung and breast), brain cell metabolism in normal and pathological conditions, stem cell metabolism along cardiac and neural differentiation, and cell metabolic response to virus infection.
Group Members
- Cristina Peixoto, PhD, Head Downstream
- António Roldão, PhD, Head Upstream and Vaccine Development
- Inês Isidro, PhD, Head Biosystems and Data Science
- Tiago Bandeiras, PhD, Invited Scientist (Res Contracts with Industry)
- Ricardo Silva, PhD, Invited Scientist (Res Contracts with Industry)
- Sofia Carvalho, PhD, Invited Scientist (Res Contracts with Industry)
- Susana Lobo, PhD Invited Scientist (Res Contracts with Industry)
- Ricardo Correia, PhD, Invited Scientist (Res Contracts with Industry)
- Barbara Fernandes, PhD, Invited Scientist (Res Contracts with Industry)
Selected Publications
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Pais DA, Portela RM, Carrondo MJ, Isidro IA, Alves PM. Enabling PAT in insect cell bioprocesses: in-situ monitoring of recombinant adeno-associated virus production by fluorescence spectroscopy. Biotechnology and Bioengineering. 2019; 116: 2803–2814. doi.org/10.1002/bit.27117
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Correia R, Fernandes B, Alves PM, Carrondo MJT, Roldão A. Improving Influenza HA-Vlps Production in Insect High Five Cells via Adaptive Laboratory Evolution. Vaccines (Basel). 2020 Oct 7;8(4):589. doi: 10.3390/vaccines8040589.
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Neto Salomé, Mendes João P., Santos Susana B. Dos, Solbrand Anita, Carrondo Manuel J. T., Peixoto Cristina, Silva Ricardo J. S.; Efficient adeno-associated virus serotype 5 capture with affinity functionalized nanofiber adsorbent, Frontiers in Bioengineering and Biotechnology, 2023; 11, DOI: 10.3389/fbioe.2023.1183974
ACT Unit Website
For further information please visit the ACT webpage
Laboratório de Engenharia Celular (PT)
Dentro da Unidade de Tecnologia de Células Animais (UTCA), o Laboratório de Engenharia Celular integra processos de produção e purificação com ferramentas físico-matemáticas de modo a desenvolver bioprocessos para obtenção de novos e complexos biofármacos. Os critérios de simplicidade, exequibilidade, transferência e economicidade surgem como essenciais para a criação de oportunidades de industrialização. A atividade iniciada no dealbar da década de noventa em proteínas com modificações pos-translacionais foi sendo alargada a vacinas (e.g. VLPs de Influenza, retro-VLPs, HIG Gag-VLPs, ZIKV-VLPs, vacinas virais…) e vetores virais para terapia génica (e.g. adenovirus, retrovirus, lentivirus, AAVs,…), baseada na competência e investigação desenvolvida pelos dois outros laboratórios da UTCA. No Laboratório de Engenharia Celular, o desenvolvimento de bioprocessos compreende a otimização de sistemas de expressão de células de mamíferos e de inseto (expressão estável ou transiente), avaliação de diferentes modos de operação de bioreator (e.g. “fed-batch” e perfusão), aplicação de modelos de redução de escala para otimização de parâmetros de produção, desenho de novos processos de purificação operados em contínuo, modelação matemática para controlo de processos biológicos e químicos, e aumento de escala para aplicações pré-clínicas. Mais recentemente, biologia de sistemas (e.g. uso de carbono marcado para estimativa de fluxos metabólicos e analise do metabolismo extracelular por 1H-NMR) tem vindo a auxiliar o desenvolvimento de bioprocessos em áreas como o metabolismo de células cancerígenas (e.g. pulmão e mama), metabolismo de células cerebrais em condições normais e patológicas, metabolismo de células estaminais ao longo da diferenciação cardíaca e neural, e resposta metabólica celular à infeção por um vírus.