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A new perspective on the metabolic pathway to neuronal dysfunction: Using organs on a chip to elucidate the role of the brain microvasculature

Periodic Reporting for period 1 - SweetBrain (A new perspective on the metabolic pathway to neuronal dysfunction: Using organs on a chip to elucidate the role of the brain microvasculature)

Reporting period: 2020-09-01 to 2022-02-28

The main goal of this project is to identify how sugar leads to neurodegeneration. This has a major impact on the society, as in recent years it was observed that there is a link between high sugar levels and neurodegenartion.
Moreover, as modern societies show huge sugar consumption, this project is especially important for reducing the health risks of sugar consumption.
To achieve this, we use state of the art-human relevant models, know as Organs-on-a-Chip, to decipher the lead of how sugar leads to neurodegeneration.

The main objectives are:
Aim 1. Establish a human-relevant NVU model for metabolic and functional interactions.
Aim 2. Identify the major metabolic and functional interactions in the human NVU at homeostasis and under diabetic conditions.
Aim 3. Target the vasculature–neuron communications to diminish neuronal dysfunction.
In the last period of research we focused on the following aims:
Platform development: – we developed a “Smart”-Organ-on-a-Chip which allows measuring the vascular functionality with spatial resolution. This work was published in Lab Chip (Renous, Noa, et al. "Spatial trans-epithelial electrical resistance (S-TEER) integrated in organs-on-chips." Lab on a Chip 22.1 (2022): 71-79). In addition, we developed a modular chip that can transform a culture well into a chip, which saves time and money and it was published in APL bioengineering (Rauti, Rossana, et al. "Transforming a well into a chip: A modular 3D-printed microfluidic chip." APL bioengineering 5.2 (2021): 026103).
Covid: During the beginning of the SweetBrain project, the world pandemic started, and we joined the world effort to get more knowledge on the pandemic. To do so, we identified which of the 29 proteins which create the SARS-Cov-2 virus, has the most significant on the vasculature. We identified that 5 proteins reduce the ability of the vasculature to protect the tissues. Furthermore, we developed a computational model to predict how each one of the SARS-Cov-2 can affect the different tissues in the body. This work was published in Elife (Rauti, Rossana, et al. "Effect of SARS-CoV-2 proteins on vascular permeability." Elife 10 (2021): e69314.).
Desimination and enriching the field: We also did three review papers which give an overview on the field. These reviews were published in Annual reviews, APL bioengineering and Cells and Tissue research: Hajal, Cynthia, et al. "Biology and Models of the Blood–brain Barrier." Annual review of biomedical engineering 23 (2021): 359-384.; Maoz, Ben M. "Brain-on-a-Chip: Characterizing the next generation of advanced in vitro platforms for modeling the central nervous system." APL bioengineering 5.3 (2021): 030902; Maoz, Ben M., et al. "Technology-based approaches toward a better understanding of neuro-coagulation in brain homeostasis." Cell and tissue research (2021): 1-6.
During the beginning of the SweetBrain project, the world pandemic started, and we joined the world effort to get more knowledge on the pandemic. To do so, we identified which of the 29 proteins which create the SARS-Cov-2 virus, has the most significant on the vasculature. We identified that 5 proteins reduce the ability of the vasculature to protect the tissues. Furthermore, we developed a computational model to predict how each one of the SARS-Cov-2 can affect the different tissues in the body. This work was published in Elife (Rauti, Rossana, et al. "Effect of SARS-CoV-2 proteins on vascular permeability." Elife 10 (2021): e69314.). This was extremely novel, as when we published our work, there were about 100,000 papers which are Covid-related, but less then 10 on the effect of Covid on the vasculature.
This had a major impact and received a lot news coverage including national and international media (news and TV).
The covid paper
Smart OoC paper