Lifeboat Foundation

The recent introduction of the breathtaking AI tool ChatGPT has sparked a national dialogue about the future of artificial intelligence in health care, education, research, and beyond. In this session, four UCSF experts discuss AI’s current and potential uses, in areas ranging from research to education to clinical care. After a brief presentation by each speaker, DOM Chair Bob Wachter moderates a far-ranging panel discussion on the health care applications of ChatGPT.

Speakers:
Atul Butte, MD, PhD, professor of Pediatrics, Bioengineering and Therapeutic Sciences, and Epidemiology and Biostatistics; director, UCSF Bakar Computational Health Sciences Institute; chief data scientist, University of California Health System.

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There are many therapies that target cancer. The most well-known is chemotherapy, which is a toxic chemical that is directed at a tumor to kill the cells. This is currently the standard of care for most types of cancer. However, as science advances, less toxic and more direct therapies are discovered. The most recently discovered therapy is known as ‘immunotherapy’, which redirects the immune system to kill the tumor. There are many successful treatments with immunotherapy among different types of cancers, including melanoma and lung cancer. Unfortunately, immunotherapy is limited in many solid tumors due to the immunosuppressive tumor microenvironment (TME). The TME is a pro-tumor environment that the cancer has made by releasing specific proteins that allow it to progress. In this environment the tumor can remain undetected from the immune system and progress throughout the body. Different immune cells in the TME become polarized and alter their functions to help the tumor proliferate and grow. It is now becoming more common to pair therapies together including immunotherapy with chemotherapy. Scientists are still trying to find ways to improve treatment and completely eradicate the tumor.

In San Francisco, California, a group of scientists, led by Dr. Alex Marson, are working to modify gene expression to reprogram or change immune cells in the TME to attack cancer. There has been some success, but this immunotherapy does not help treat all patients. In addition, the screening process to determine genetic changes to determine which cells would result in the greatest treatment efficacy is a long, arduous process. A group at the Gladstone Institutes has worked with Marson at University of California San Francisco (UCSF) to develop a strategy that helps pair different genetic combinations in a faster amount of time to determine the most beneficial treatment outcomes. This screening technique is called Pooled Knockin Screening (ModPoKI). ModPoKI finds the best genetic modifications to express in immune cells that will have prolonged anti-tumor efficacy.

The study that demonstrated ModPoKI was published recently in Cell, which demonstrates our ability to now understand how to combine genetic programs. ModPoKI combines genes into long lines of DNA to generate roughly 10,000 combinations to match with a genetically engineered immune cell known as a T cells are major immune cells that primarily target foreign antigens, like cancer cells, and kill them. Once the optimal gene modification is found, it is put into the engineered immune cells that are polarized to kill cancer. After further investigation, the combinations made by ModPoKI resulted in the most polarized anti-tumor T cells.

One proven method for tracking down the genetic origins of diseases is to knock out a single gene in animals and study the consequences this has for the organism. The problem is that for many diseases, the pathology is determined by multiple genes, complicating the task for scientists trying to pinpoint the contribution of any single gene to the condition. To do this, they would have to perform many animal experiments – one for each desired gene modification.

Researchers led by Randall Platt, Professor of Biological Engineering at the Department of Biosystems Science and Engineering at ETH Zurich in Basel, have now developed a method that will greatly simplify and speed up research with laboratory animals: using the CRISPR-Cas gene scissors, they simultaneously make several dozen gene changes in the cells of a single animal, much like a mosaic.

While no more than one gene is altered in each cell, the various cells within an organ are altered in different ways. Individual cells can then be precisely analyzed. This enables researchers to study the ramifications of many different gene changes in a single experiment.

Discovering And Developing Medicines To Keep You Biologically Young — Dr. Marco Quarta, Ph.D. — Co-Founder and CEO, Rubedo Life Sciences; CEO, Phaedon Institute.

Dr. Marco Quarta, Ph.D. is Co-Founder and CEO of Rubedo Life Sciences (https://www.rubedolife.com/), a biopharmaceutical company developing a broad portfolio of innovative therapies engineered to target cells which drive chronic age-related diseases. The company’s proprietary ALEMBIC™ drug discovery platform has engineered novel first-in-class small molecules designed to selectively target senescent cells, which play a key role in the progression of pulmonary, dermatological, oncological, neurodegenerative, fibrotic and other chronic disorders.

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Many biological processes depend on chemical reactions that are localized in space and time and therefore require catalytic components that self-organize. The collective behavior of these active particles depends on their chemotactic movement—how they sense and respond to chemical gradients in the environment. Mixtures of such active catalysts generate complex reaction networks, and the process by which self-organization emerges in these networks presents a puzzle. Jaime Agudo-Canalejo of the Max Planck Institute for Dynamics and Self-Organization, Germany, and his colleagues now show that the phenomenon of self-organization depends strongly on the network topology [1]. The finding provides new insights for understanding microbiological systems and for engineering synthetic catalytic colloids.

In a biological metabolic network, catalysts convert substrates into products. The product of one catalyst species acts as the substrate for another species—and so on. Agudo-Canalejo and his team modeled a three-species system. First, building on a well-established continuum theory for catalytically active species that diffuse along chemical gradients, they showed that systems where each species responds chemotactically only to its own substrate cannot self-organize unless one species is self-attracting. Next, they developed a model that allowed species to respond to both their substrates and their products. Pair interactions between different species in this more complex model drove an instability that spread throughout the three-species system, causing the catalysts to clump together. Surprisingly, this self-organization process occurred even among particles that were individually self-repelling.

The researchers say that their discovery of the importance of network topology—which catalyst species affect and are affected by which substrates and products—could open new directions in studies of active matter, informing both origin-of-life research and the design of shape-shifting functional structures.

The intricate interplay of gene expression within living cells is akin to a well-orchestrated symphony, with each gene playing its part in perfect harmony to ensure cells function as they should. At the heart of this symphony are transcription factors (TFs), molecular maestros that regulate the expression of genes by binding to specific DNA sequences known as promoters.

Unlocking the secrets of these genome-scale regulatory networks requires a comprehensive collection of gene expression profiles, but measuring gene expression responses for every TF and promoter pair has posed a formidable challenge due to the sheer number of potential combinations, even in relatively simple organisms such as bacteria.

To tackle this challenge, researchers led by Fuzhong Zhang, professor of energy, environmental & chemical engineering in the McKelvey School of Engineering at Washington University in St. Louis, developed a technique called pooled promoter responses to TF perturbation sequencing (PPTP-seq).

Summary: The revolutionary field of bio-computing is making waves as DishBrain, a neural system combining 800,000 living brain cells, learns to play Pong. Recognizing the pressing need for ethical guidelines in this emerging domain, the pioneers behind DishBrain have joined forces with bioethicists in a study.

The research explores the moral considerations around biological computing systems and their potential consciousness. Beyond its innovation, the technology offers vast environmental benefits, potentially transforming the energy-consuming IT industry.

Conventional manufacturing methods such as soft lithography and hot embossing processes can be used to bioengineer microfluidic chips, albeit with limitations, including difficulty in preparing multilayered structures, cost-and labor-consuming fabrication processes as well as low productivity.

Materials scientists have introduced digital light processing as a cost-effective microfabrication approach to 3D print microfluidic chips, although the fabrication resolution of these microchannels are limited to a scale of sub-100 microns.

In a new report published in Microsystems and Nanoengineering, Zhuming Luo and a scientific team in biomedical engineering, and chemical engineering in China developed an innovative digital light processing method.

When you think about it, it seems impossible: a microscope so small and lightweight you can carry it like a keychain. But enter the Make-roscope, an invention of Jeremy De Leon, a 28-year-old Manufacturing Engineering graduate of Mapua University.

Used with a smartphone or tablet—simply place the Make-roscope on top of the gadget’s front camera—the invention can magnify organisms up to 400 times. And because it is made of food-grade silicone and a special type of lens, it is also handy, waterproof, and will be good to use for a very long time. While the principles behind pocket microscopes already exist, Jeremy’s new design innovation provides better ease of use.

Jeremy’s Make-roscope kit, which includes an information card, tweezers, keychain, cleaning cloth, blank glass slides, prepared specimen, pipette, specimen tubes, and cotton swabs, won the biggest prize in the Philippine leg of the James Dyson Award out of 47 entries from 12 universities. Jeremy says he will use the P330,000 prize money to further develop his invention.