Retrospective: Marilyn Farquhar (1928 – 2019)
The passing of Marilyn Farquhar on Nov. 23 brought to a close a long and inspiring career in cell biology. She rightly ranks among the pioneers in her field and especially as a role model for women in science.
Human Gut-in-a-Dish Model Helps Define ‘Leaky Gut,’ and Outline a Pathway to Treatment
Once a vague scapegoat for a variety of ills, increasing evidence suggests a condition known as “leaky gut” — in which microbes and other molecules seep out of the intestines — may be more common, and more harmful, than previously thought.

University of California San Diego School of Medicine researchers are now able to simulate leaky gut conditions for the first time, using 3D models of human intestines generated from patient cells. These small organoids, or “mini-guts,” have revealed new biomarkers that help define what a leaky gut looks like — molecular signals that could one day help clinicians better diagnose the condition, track its progression and evaluate the success or failure of treatments.

The study, published February 10, 2020 in Life Science Alliance , was led by first author Pradipta Ghosh, MD, professor of cellular and molecular medicine at UC San Diego School of Medicine and Moores Cancer Center, and senior author Soumita Das, PhD, associate professor of pathology at UC San Diego School of Medicine.
Stem Cells, CRISPR and Gene Sequencing Technology are Basis of New Brain Cancer Model
Using genetically engineered human pluripotent stem cells, University of California San Diego School of Medicine researchers created a new type of cancer model to study in vivo how glioblastoma, the most common and aggressive form of brain cancer, develops and changes over time.

Reporting in the January 28, 2020 issue of Nature Communications, researchers used CRISPR editing to make precise mutations in an otherwise “normal” genome to create the genetic conditions that enable tumor development. The resulting avatars are unique in that they behave like a grade 4 glioma — a fast-growing type of tumor that starts in the glial cells of the brain — in their level of pathology, transcriptome signatures, engineered genetic alterations and evolution of genetic mutations, such as the emergence of extrachromosomal DNA and chromosomal rearrangements.

“The addition of single-cell RNA sequencing and computational tools enabled efficient analysis of big data to truly evaluate the surprising intra-tumor heterogeneity present in our avatars which replicates what is seen in patients samples,” said co-senior author Gene W. Yeo, PhD, professor in the Department of Cellular and Molecular Medicine and the Institute for Genomic Medicine at UC San Diego and faculty member in the Sanford Consortium for Regenerative Medicine.
How to Be Humane to a Lab-Grown Brain
The study of brain organoids can be fraught with ethical dilemmas. “In order for it to be a good model, you want it to be as human as possible,” said Hank Greely, a law professor at Stanford University who specializes in ethical and legal issues in the biosciences. “But the more human it gets, the more you’re backing into the same sorts of ethics questions that are the reasons why you can’t just use living humans.”

Ethicists and scientists are now working together to figure out whether organoids warrant their own rules. The ethical discussions are progressing at a fast clip, well ahead of the science. The National Institutes of Health has sponsored meetings and workshops, and there’s been talk of creating another kind of oversight committee. Scientists have reached out privately to ethicists to discuss the particulars of their research, and Alysson Muotri, PhD, a biologist at UC San Diego, has organized conferences to connect ethicists with both stem cell biologists and consciousness researchers.
Disembodied Brains Are Scary Or How Sci-Fi Influences Science
I wanted to visit a scientist in his lab in order to explore how science and science fiction inspire each other, and where scientists get their ideas from. The person I visited was UC San Diego professor and neuroscientist Alysson Muotri, PhD, who uses stem cells to study the brain...
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