Tuesday, 22 September 2020

Artificial cells drive neural differentiation

A research team led by UniTrento has developed artificial cells capable of communicating with neuronal cells and of guiding their differentiation

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A new study coordinated by the University of Trento and funded by the Armenise Harvard Foundation developed artificial cells that are capable of differentiating neurons. The work, which was published in Science Advances, demonstrates that cellular mimics built in laboratory can communicate with living neurons and talk them into differentiating themselves. This approach can have a significant impact on the use of artificial cells for therapeutic purposes.

The research project involves four teams of the Cibio Department of the University of Trento, and specifically the laboratories run by Sheref Mansy, Marie-Laure Baudet, Luciano Conti and Paolo Macchi. The former two have both received a Career Development Award (CDA) by the Armenise Harvard Foundation, which provided funding for the research project. Other participating partners are the National Research Council and the University of Alberta (Canada). The researchers combined neuroscience and artificial intelligence with cellular biology.

“Duhan Toparlak, a postdoc of my laboratory, built the artificial cells. In the new study, we saw that these artificial cells can perceive a physiological signal and, to respond to it, they release a specific protein signal which drives the differentiation of neuronal cells", commented Sheref Mansy, the US-born biochemist who leads the project. Mansy moved to Trento in 2009 after receiving the Career Development Award from the Armenise-Harvard Foundation. He is the head of the Origins of Life and Synthetic Biology Lab at CIBIO of the University of Trento, and a professor of the Chemistry Department of the University of Alberta.

Sheref Mansy's team worked side by side with the teams of Marie-Laure Baudet, Luciano Conti and Paolo Macchi, who lead, respectively, the Armenise-Harvard Axonal Neurobiology laboratory, the Stem Cell Biology laboratory and the Molecular and Cellular Neurobiology laboratory.
The scientists established that the artificial cells could elicit the desired changes in neural stem cells, including their differentiation.

“My laboratory participated in the study by sharing our expertise in brain stem cells, and by integrating the expertise provided by Sheref Mansy in the area of synthetic biology and of Marie-Laure Baudet on axonal development. For the first time we engineered artificial cells to drive and support the biological processes required to turn brain stem cells into mature neurons, which was thrilling” said Luciano Conti, professor of applied biology and an expert in stem cells. After positions at the University of Milan and in Great Britain, Conti has been doing research in Trento since 2013. His work achieved important results as regards the production of brain stem cells and neurons from pluripotent stem cells and cerebral tissue.

“Sheref Mansy contacted Luciano Conti and me so that we could put our knowledge together. We jointly developed a strategy to create artificial cells capable of sending messages to neurons. We then defined a biological interpretation to reveal that the message was actually received by biological cells. It seemed impossible, but our teams together managed to speed up the growth of axons and to prompt the differentiation and survival of neural stem cells, which can have a huge impact at clinical level", commented Marie-Laure Baudet, head of the Armenise-Harvard Axonal Neurobiology laboratory. A French biologist and recipient of the CDA Armenise Harvard in 2012, Marie-Laure Baudet moved to Trento after holding positions in Canada and Great Britain. In her career at the Cibio Department of the University of Trento she identified one of the crucial processes in the development of neuronal connections, which was also involved in the new study featured in Science Advances. The development of connections among neurons is absolutely essential during brain development. A failure in this phase, during the creation of the circuits, can have devastating consequences and may lead to serious neurological disorders.

For this reason, driving neurons to perform key functions like differentiation from genetically controlled artificial cells can have great therapeutic applications to fight neurodegenerative diseases. The technology developed in this study will one day open the way to artificial cells capable of synthesizing and delivering specific therapeutic molecules tailored to distinct physiological conditions.

The Armenise Harvard Foundation
The Foundation was established in 1996 by Giovanni Auletta Armenise to support basic biomedical research. Its mission is to help young scientists working abroad establish their laboratory in Italy, and it supports various research programmes at the Harvard Medical School in Boston. The Foundation so far invested over 70 million dollars at Harvard and 31 million dollars in Italian research, fostering research projects and scientific collaborations across the Atlantic. The Career Development Award (CDA) amounts to 200,000 USD per year (for 3 to 5 years) and so far benefited 27 young scientists who opened their laboratories in Italy. With 5 researchers who received the grant in the past decade, the University of Trento is the institution counting more awardees together with San Raffaele in Milan.

About the article
Ö. Duhan Toparlak, Jacopo Zasso, Simone Bridi, Mauro Dalla Serra, Paolo Macchi, Luciano Conti, Marie-Laure Baudet, Sheref S. Mansy, “Artificial cells drive neural differentiation”, Science Advances, Vol. 6, no. 38, DOI: 10.1126/sciadv.abb4920