May 3, 2017 The cover image of the MCB journal. Credit: IDIBELL

Researchers from the Cell death group of the Bellvitge Biomedical Research Institute (IDIBELL), led by Dr. Cristina Muoz-Pinedo, have characterized the cell death process due to starvation, in which the endoplasmic reticulum plays a leading role. Their work, chosen as the cover of the latest Molecular and Cellular Biology journal, was carried out within TRAIN-ERs, a European collaborative action that studies diseases associated with this cellular organelle.

"Usually, programmed cell deathalso called apoptosisfollows a biochemical pathway related to the permeabilization of mitochondria; However, we observed that in cases of cell death due to lack of glucose, cells die in an unexpected way, following a process similar to what we would expect from an immune response", explains Dr. Cristina Muoz-Pinedo, last author of the study.

In cell-death-related treatments such as chemotherapy, the mitochondrial pathway is activated. Instead, when starved, cells activate the so-called "death receptors" on their membrane, which are normally used by the lymphocytes of the immune system to attack and destroy infected cells.

IDIBELL researchers have been able to relate the activation of these membrane receptors to the endoplasmic reticulum, a cellular organelle involved in protein synthesis and lipid metabolism, as well as intracellular transport. "Feeling the stress produced by the lack of nutrients, the reticulum send an alarm signal that triggers the appearance of death receptors in the membrane", says Dr. Muoz-Pinedo.

"According to our in vitro results, we assume that this is how the tumor cells located in the center of a tumorthe so-called necrotic coredie, because there are never enough nutrients in those areas", adds the IDIBELL researcher. "On the other hand, in ischemia, besides the lack of oxygen there is also cell death due to lack of glucose, so this process could also be related to the activity of the endoplasmic reticulum at a biochemical level".

Explore further: Scientists reveal alternative route for cell death

More information: Raffaella Iurlaro et al, Glucose Deprivation Induces ATF4-Mediated Apoptosis through TRAIL Death Receptors, Molecular and Cellular Biology (2017). DOI: 10.1128/MCB.00479-16

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Starvation causes atypical cell death - Phys.Org

For USC Stem Cell researcher Leonardo Morsut, the word set refers to a collection of scientific data. Set is also the prelude to spiking a volleyball over the net something he used to do for a living as a professional athlete in Italy.

Morsut in action on the volleyball court (Photo/Courtesy of Leonardo Morsut)

In my mind, professional volleyball was always a side project, said Morsut, who played for seven years for the professional teams in his hometown of Padova and in Trentino. It was science that was the main thing.

True to his words, Morsut has always put research first. Even while playing pro volleyball for seven hours a day, he found the time and energy to attend the University of Padova, where Galileo was once a lecturer. Morsut earned bachelors and masters degrees in medical biotechnologies before pursuing a second bachelors in mathematics.

Then, at age 25, at the peak of his volleyball career, he quit. He walked away from fame and a handsome salary to lead the humble life of a PhD student at the University of Padova. His decision made national headlines in Italy.

People ask me if I regretted it, he said. I dont even think about leaving that way. There wasnt really a turning point. There was just one path.

As a PhD student, he pursued research in bioscience, genetics and the molecular biology of development. He spent years focused on mouse gastrulation, the early embryonic phase during which a ball of cells organizes itself into distinct layers as a prelude to organ formation.

In the midst of this research, he picked up an unrelated side project: how stem cells behave differently depending upon whether theyre on a hard or a soft surface. Specifically, he and his colleagues found that when stem cells are on a hard surface, they react by producing two signals called YAP and TAZ that encourage them to become bone cells. The side project quickly became his main project, and Morsut and his team published their discovery in the journal Nature.

It was really a rush and a blast, Morsut said. And it was what launched my career because then it was easier to get a postdoc in a bigger lab.

After receiving his PhD and spending an additional postdoctoral year at the University of Padova, he became increasingly fascinated by the emerging field known as synthetic biology.

Synthetic biology is pretty much trying to bring the engineering approach of building things into biology.

Leonardo Morsut

Synthetic biology is pretty much trying to bring the engineering approach of building things into biology, Morsut said. You think about the biological system not as something that you want to learn about, but as something that you want to use to achieve a goal.

Inspired by this approach, he accepted a postdoctoral fellowship in the lab of one of the founders of synthetic biology: Wendell Lim at the University of California, San Francisco.

Wendell and I didnt even know what I was going to work on, but we liked each other, Morsut said.

After some early experimentation, Morsut settled on his main project: building a synthetic cellular communication system known as synNotch, which enables scientists to direct the behavior of cells in useful ways.

Morsut created synNotch by co-opting a relatively simple natural communication system, called Notch, in which a cell uses a sensor on its surface to recognize and trigger a particular response to a specific signal. In Morsuts synthetic version of Notch, he swapped in a new sensor, allowing him to control which signal the sensor recognizes, as well as what the cell does in response.

SynNotch or a similar system could have many potential medical applications. For example, scientists could swap in a sensor that enables an immune cell to recognize a signal from a tumor and then respond with an attack. Alternatively, researchers could use this technology to prompt cells to differentiate and organize into tissues with special properties, such as enhanced injury resistance or regenerative capacity.

The breakthrough earned Morsut a position as the newest assistant professor of stem cell biology and regenerative medicine at USC. At the same time, his wife Sabina accepted a postdoctoral fellowship in art history at the university. Other big changes are on the horizon: The couple, who originally met when they were 12 years old in their hometown of Padova, will expand their family with the arrival of their second child in June.

When hes not enjoying his family or building tissues in the lab, Morsut can be found on the yoga mat, developing his meditation and hatha yoga practice under Yogarupa Rod Stryker.

As he starts his own lab at USC, Morsut plans to use synNotch to direct the differentiation of stem cells into blood vessels, which can supply oxygen and nutrients to engineered tissues and organs in the future. He is also working to develop additional synthetic biology tools and looks forward to collaborating with researchers from across the university, especially at the USC Viterbi School of Engineering and the USC Michelson Center for Convergent Bioscience, slated to open this fall.

The stem cell department is very exciting, and it has a lot of potential and a lot of forward thinking, Morsut said. Engineering is also a strength of USC, and there is interest on both sides to grow more at that interface. That is definitely something that will benefit my research program and vice versa. I have high expectations.

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