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Category: bioengineering – Page 84

Bioelectric Networks: Taming the Collective Intelligence of Cells for Regenerative Medicine

Seminar summary: https://foresight.org/summary/bioelectric-networks-taming-th…-medicine/
Program & apply to join: https://foresight.org/biotech-health-extension-program/

Foresight Biotech & Health Extension Meeting sponsored by 100 Plus Capital.

Michael Levin, Tufts Center for Regenerative and Developmental Biology.
Bioelectric Networks: Taming the Collective Intelligence of Cells for Regenerative Medicine.

Michael Levin, Distinguished Professor in the Biology department and Vannevar Bush Chair, serves as director of the Tufts Center for Regenerative and Developmental Biology. Recent honors include the Scientist of Vision award and the Distinguished Scholar Award. His group’s focus is on understanding the biophysical mechanisms that implement decision-making during complex pattern regulation, and harnessing endogenous bioelectric dynamics toward rational control of growth and form. The lab’s current main directions are:

• Understanding how somatic cells form bioelectrical networks for storing and recalling pattern memories that guide morphogenesis;
• Creating next-generation AI tools for helping scientists understand top-down control of pattern regulation (a new bioinformatics of shape); and.
• Using these insights to enable new capabilities in regenerative medicine and engineering.

Prior to college, Michael Levin worked as a software engineer and independent contractor in the field of scientific computing. He attended Tufts University, interested in artificial intelligence and unconventional computation. To explore the algorithms by which the biological world implemented complex adaptive behavior, he got dual B.S. degrees, in CS and in Biology and then received a PhD from Harvard University. He did post-doctoral training at Harvard Medical School (1996−2000), where he began to uncover a new bioelectric language by which cells coordinate their activity during embryogenesis. His independent laboratory (2000−2007 at Forsyth Institute, Harvard; 2008-present at Tufts University) develops new molecular-genetic and conceptual tools to probe large-scale information processing in regeneration, embryogenesis, and cancer suppression.

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Will Microbes Replace Machines?

Just when we are getting accustomed to artificial intelligence in our daily lives, get ready for a new disruptor: synthetic biology, or syn-bio, the design and engineering of biological systems to create and improve processes and products. It promises to become a manufacturing paradigm of the future.

Recent advances in molecular, cell, and systems biology have enabled scientists to shift their focus from research of syn-bio to design and engineering, creating some truly mind blowing applications. By using microorganisms, for example, companies can now manufacture an infinite number of things, cell by cell, from scratch. This offers new ways of producing almost everything that humans consume, from flavors and fabrics to foods and fuels.

By the end of the decade, syn-bio may be used extensively in manufacturing industries that account for more than a third of global output, according to BCG Henderson Institute, Boston Consulting Group’s strategy think tank. Various sources estimate that the syn-bio market today is about $10 billion and is expected to reach $30 billion in the next five years.

First-of-its-kind instrument officially ushers in new era of X-ray science

Arizona State University has officially begun a new chapter in X-ray science with a newly commissioned, first-of-its-kind instrument that will help scientists see deeper into matter and living things. The device, called the compact X-ray light source (CXLS), marked a major milestone in its operations as ASU scientists generated its first X-rays on the night of Feb. 2.

“This marks the beginning of a new era of science with compact accelerator-based X‑ray sources,” said Robert Kaindl, who directs ASU’s Compact X-ray Free Electron Laser (CXFEL) Labs at the Biodesign Institute and is a professor in the Department of Physics. “The CXLS provides hard X-ray pulses with high flux, stability and ultrashort durations, in a very compact footprint. This way, matter can be resolved at its fundamental scales in space and time, enabling new discoveries across many fields — from next-generation materials for computing and information science, to renewable energy, biomolecular dynamics, drug discovery and human health.”

Building the compact X-ray light source is the first phase of a larger CXFEL project, which aims to build two instruments including a coherent X-ray laser. As the first-stage instrument, the ASU CXLS generates a high-flux beam of hard X‑rays, with wavelengths short enough to resolve the atomic structure of complex molecules. Moreover, its output is pulsed at extremely short durations of a few hundred femtoseconds — well below a millionth of one millionth of a second — and thus short enough to directly track the motions of atoms.

Engineering Cyborg Bacteria Through Intracellular Hydrogelation

Synthetic biology has made major strides towards the holy grail of fully programmable bio-micromachines capable of sensing and responding to defined stimuli regardless of their environmental context. A common type of bio-micromachines is created by genetically modifying living cells.[ 1 ] Living cells possess the unique advantage of being highly adaptable and versatile.[ 2 ] To date, living cells have been successfully repurposed for a wide variety of applications, including living therapeutics,[ 3 ] bioremediation,[ 4 ] and drug and gene delivery.[ 5, 6 ] However, the resulting synthetic living cells are challenging to control due to their continuous adaption and evolving cellular context. Application of these autonomously replicating organisms often requires tailored biocontainment strategies,[ 7-9 ] which can raise logistical hurdles and safety concerns.

In contrast, nonliving synthetic cells, notably artificial cells,[ 10, 11 ] can be created using synthetic materials, such as polymers or phospholipids. Meticulous engineering of materials enables defined partitioning of bioactive agents, and the resulting biomimetic systems possess advantages including predictable functions, tolerance to certain environmental stressors, and ease of engineering.[ 12, 13 ] Nonliving cell-mimetic systems have been employed to deliver anticancer drugs,[ 14 ] promote antitumor immune responses,[ 15 ] communicate with other cells,[ 16, 17 ] mimic immune cells,[ 18, 19 ] and perform photosynthesis.

Gene editing company plans to resurrect the dodo

Colossal Biosciences, a genetic engineering company focused on de-extincting past species, has announced $150 million in Series B funding, which it plans to use for bringing back the iconic dodo.

The resurrection of several extinct species is predicted to occur within the next five years. One company aiming to make that a reality is Texas-based startup Colossal Biosciences, founded in 2021 by some of the world’s leading experts in genomics. In May 2022, it appeared in the World Economic Forum’s list of Technology Pioneers and it won Genomics Innovation of the Year at the BioTech Breakthrough Awards.

A cnidarian parasite of salmon (Myxozoa: Henneguya) lacks a mitochondrial genome

Year 2020 This type of parasite that feeds on salmon actually doesn’t need oxygen to live. Which means eventually there could be even gene editing that could essentially allow humans to not need as much air or could be independent of oxygen but only need anaerobic metabolisms perhaps. Really this can only expand our understanding of new ways to evolve humans to the next level.

Although aerobic respiration is a hallmark of eukaryotes, a few unicellular lineages, growing in hypoxic environments, have secondarily lost this ability. In the absence of oxygen, the mitochondria of these organisms have lost all or parts of their genomes and evolved into mitochondria-related organelles (MROs). There has been debate regarding the presence of MROs in animals. Using deep sequencing approaches, we discovered that a member of the Cnidaria, the myxozoan Henneguya salminicola, has no mitochondrial genome, and thus has lost the ability to perform aerobic cellular respiration. This indicates that these core eukaryotic features are not ubiquitous among animals. Our analyses suggest that H. salminicola lost not only its mitochondrial genome but also nearly all nuclear genes involved in transcription and replication of the mitochondrial genome. In contrast, we identified many genes that encode proteins involved in other mitochondrial pathways and determined that genes involved in aerobic respiration or mitochondrial DNA replication were either absent or present only as pseudogenes. As a control, we used the same sequencing and annotation methods to show that a closely related myxozoan, Myxobolus squamalis, has a mitochondrial genome. The molecular results are supported by fluorescence micrographs, which show the presence of mitochondrial DNA in M. squamalis, but not in H. salminicola. Our discovery confirms that adaptation to an anaerobic environment is not unique to single-celled eukaryotes, but has also evolved in a multicellular, parasitic animal. Hence, H. salminicola provides an opportunity for understanding the evolutionary transition from an aerobic to an exclusive anaerobic metabolism.

Genetic engineering sheds light on ancient evolutionary questions

Cyanobacteria are single-celled organisms that derive energy from light, using photosynthesis to convert atmospheric carbon dioxide (CO2) and liquid water (H2O) into breathable oxygen and the carbon-based molecules like proteins that make up their cells. Cyanobacteria were the first organisms to perform photosynthesis in the history of Earth, and were responsible for flooding the early Earth with oxygen, thus significantly influencing how life evolved.

Geological measurements suggest that the atmosphere of the early Earth—over three billion years ago—was likely rich in CO2, far higher than current levels caused by , meaning that ancient had plenty to “eat.”

But over Earth’s multi-billion-year history, atmospheric CO2 concentrations have decreased, and so to survive, these bacteria needed to evolve new strategies to extract CO2. Modern cyanobacteria thus look quite different from their ancient ancestors, and possess a complex, fragile set of structures called a CO2-concentrating mechanism (CCM) to compensate for lower concentrations of CO2.

AAV Manufacturing Sees Big Opportunities in Synthetic Biology

My recently published perspective paper has been featured by GEN Genetic Engineering & Biotechnology News!

#biotechnology #genetherapy #syntheticbiology

Synthetic biology has the potential to upend existing paradigms of adeno-associated virus (AAV) production, helping to reduce the high costs of gene therapy and thus make it more accessible, according to a recent paper.

AAVs are an important vector for gene therapy, but AAV manufacturing is complex and expensive. Furthermore, first author Logan Thrasher Collins, a PhD candidate at Washington University in Saint Louis, tells GEN. “Many current industry approaches to enhancing AAV yields involve incremental process optimization. Synthetic biology has the potential to offer more radical improvements, yet is relatively underappreciated in the context of AAV production.”

Large-scale production poses challenges not typically found during preclinical stages, such as batch-to-batch variations in plasmid yield and purity, and poor yields from producer cells, the research team notes. Likewise, downstream processing challenges also are present, such as AAV aggregation, chemical lysis, and filtration complications. The rational approach to AAV design offered by synthetic biology, however, enables scientists to programmably design systems that assemble complex macromolecular structures and to avoid—or at least minimize—many of those challenges.

Healthier hearts? Research advances potential treatment for cardiac conditions

A team of researchers from Illinois Institute of Technology and the University of Washington is trying to change the way that the field of biology understands how muscles contract.

In a paper published on January 25, 2023, in the Proceedings of the National Academy of Sciences titled “Structural OFF/ON Transition of Myosin in Related Porcine Myocardium Predict Calcium Activated Force,” Illinois Tech Research Assistant Professor Weikang Ma and Professor of Biology and Physics Thomas Irving—working in collaboration with Professor of Bioengineering Michael Regnier’s group at Washington—make the case for a second, newly discovered aspect to muscle contraction that could play a significant role in developing treatments for inherited cardiac conditions.

The consensus for how muscle contraction occurs has been that the relationship between the thin and thick filaments that comprise was a more straightforward process. When targets on thin filaments were activated, it was thought that the myosin motor proteins that make up the thick filaments would automatically find their way to those thin filaments to start generating force and contract the muscle.

Scientists Develop a Cancer Vaccine to Simultaneously Kill and Prevent Brain Cancer

Cancer vaccines are an active area of research for many labs, but the approach that Shah and his colleagues have taken is distinct. Instead of using inactivated tumor cells, the team repurposes living tumor cells, which possess an unusual feature. Like homing pigeons returning to roost, living tumor cells will travel long distances across the brain to return to the site of their fellow tumor cells. Taking advantage of this unique property, Shah’s team engineered living tumor cells using the gene editing tool CRISPR-Cas9 and repurposed them to release tumor cell killing agents. In addition, the engineered tumor cells were designed to express factors that would make them easy for the immune system to spot, tag, and remember, priming the immune system for a long-term anti-tumor response.

The team tested their repurposed CRISPR-enhanced and reverse-engineered therapeutic tumor cells (ThTC) in different mice strains, including the one that bore bone marrow, liver, and thymus cells derived from humans, mimicking the human immune microenvironment. Shah’s team also built a two-layered safety switch into the cancer cell, which, when activated, eradicates ThTCs if needed. This dual-action cell therapy was safe, applicable, and efficacious in these models, suggesting a roadmap toward therapy. While further testing and development is needed, Shah’s team specifically chose this model and used human cells to smooth the path of translating their findings for patient settings.

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