Synthetic Biology – Stemify News

The Secret to Clustering? Unveiling the Mystery Behind Spinal Cancer Clusters

Biotech, Medicine, Science, Technology / By Daniel Yakuboff

According to the CDC, over 600,000 people passed away from this leading cause of death, making it the second greatest claimant of casualties. Upon being diagnosed, one experiences a lifetime of stress and a load of rigorous treatment in the form of chemotherapy in an attempt to kill all the cells before the illness could spread to the remainder of the body. It doesn’t always stop at this point though, many go on to have progressing stages that may either require more treatment, a verdict of ‘X months to live,’ or the first followed by the second. This illness is cancer.

There are over a hundred and fifty types of cancer, ranging from the head to the toe and everything in between. Some cancers are heavily influenced by gender (such as breast cancer), others by age (such as prostate cancer), and so on and so forth. The specific one that ought to be highlighted though for its increased presence (clustering) of cancerous cells relative to the body is spinal cancer. Although most (if not all) cancers have the ability to cluster its cells in a couple of specific areas, this one can cause cancer cells to become three to five times more apparent in the spine relative to other limbs.

Without the assistance of modern medicine and technology necessary to probe deeper, scientists just considered this specific clustering of cells a medical mystery.

But we have access to that technology now. At least, researchers from Weill Cornell Medicine and the Hospital for Special Surgery in New York do. With these resources, they were available to figure out what exactly causes these clusters to emerge: vertebral skeletal stem cells in the spine. What makes these stem cells unique relative to other ones is their production of a protein that attracts these tumor (cancerous) cells to come to them.

So what can be done with this? Excellent question.

Through identifying what may exactly cause this clustering, researchers can work on targeting these vertebral skeletal stem cells to disrupt their function (i.e., attracting cancerous tumor cells to them).

That seems like the perfect plan, no? However, when an experiment on mice where these cells are targeted took place, it didn’t completely eliminate the amount of bone (and, by extension, the number of cancerous cells) in that area. This then begs the question: is there a second stem cell type that we aren’t accounting for? Or is it something else?

Sources

https://www.cdc.gov/nchs/fastats/leading-causes-of-death.htm
https://www.washingtonpost.com/science/2023/11/28/new-stem-cell-spine-cancer/
https://pubmed.ncbi.nlm.nih.gov/37704733/

Quantum-Inspired AI model helps CRISPR Cas9 Genome Editing for Microbes

Artificial Intelligence, Biology, Biotech, Medicine, Science, Technology / By Ahmed Aldeeb

A team of scientists at the Oak Ridge National Laboratory (ORNL), have embarked on a groundbreaking venture, leveraging quantum biology, artificial intelligence (AI), and bioengineering to revolutionize the effectiveness of CRISPR Cas9 genome editing tools. Their focus is on microbes, particularly those earmarked for modifications to produce renewable fuels and chemicals, presenting a unique challenge due to their distinct chromosomal structures and sizes.

Traditionally, CRISPR tools have been tailored for mammalian cells and model species, resulting in weak and inconsistent efficiency when applied to microbes. Recognizing this limitation, Carrie Eckert, leader of the Synthetic Biology group at ORNL, remarked, “Few have been geared towards microbes where the chromosomal structures and sizes are very different.” This realization prompted the ORNL scientists to explore a new frontier in the quest to enhance the precision of CRISPR tools.

The team’s journey took an unconventional turn as they delved into quantum biology, a field at the intersection of molecular biology and quantum chemistry. Quantum biology explores the influence of electronic structure on the chemical properties and interactions of nucleotides, the fundamental building blocks of DNA and RNA, within cell nuclei where genetic material resides.

To improve the modeling and design of guide RNA for CRISPR Cas9, the scientists developed an explainable AI model named the iterative random forest. Trained on a dataset of approximately 50,000 guide RNAs targeting the genome of E. coli bacteria, the model took into account quantum chemical properties. The objective was to understand, at a fundamental level, the electronic distribution in nucleotides, which influences the reactivity and stability of the Cas9 enzyme-guide RNA complex.

“The model helped us identify clues about the molecular mechanisms that underpin the efficiency of our guide RNAs,” explained Erica Prates, a computational systems biologist at ORNL. The iterative random forest, with its thousands of features and iterative nature, was trained using the high-performance Summit supercomputer at ORNL’s Oak Ridge Leadership Computer Facility.

What sets this approach apart is its commitment to explainable AI. Rather than relying on a “black box” algorithm that lacks interpretability, the ORNL team aimed to understand the biological mechanisms driving results. Jaclyn Noshay, a former ORNL computational systems biologist and first author on the paper, emphasized, “We wanted to improve our understanding of guide design rules for optimal cutting efficiency with a microbial species focus.”

**Graphical Abstract** https://academic.oup.com/nar/article/51/19/10147/7279034

Validation of the explainable AI model involved CRISPR Cas9 cutting experiments on E. coli, using a large group of guides selected by the model. The results were promising, confirming the efficacy of the model in guiding genome modifications for microbes.

The implications of this research extend far beyond microbial genome editing. “If you’re looking at any sort of drug development, for instance, where you’re using CRISPR to target a specific region of the genome, you must have the most accurate model to predict those guides,” highlighted Carrie Eckert. The study not only advances the field of synthetic biology but also has broader applications in drug development and bioenergy research.

The ORNL researchers envision collaborative efforts with computational science colleagues to further enhance the microbial CRISPR Cas9 model using additional data from lab experiments and diverse microbial species. The ultimate goal is to refine CRISPR Cas9 models for a wide range of species, facilitating predictive DNA modifications with unprecedented precision.

The study, supported by the DOE Office of Science Biological and Environmental Research Program, ORNL’s Lab-Directed Research and Development program, and high-performance computing resources, signifies a significant leap forward in the quest to improve CRISPR technology. As Paul Abraham, a bioanalytical chemist at ORNL, remarked, “A major goal of our research is to improve the ability to predictively modify the DNA of more organisms using CRISPR tools. This study represents an exciting advancement toward understanding how we can avoid making costly ‘typos’ in an organism’s genetic code.” The findings hold promise for applications in fields ranging from bioenergy feedstock enhancement to drug development, marking a pivotal moment in the evolution of CRISPR technology.

Sources

https://doi.org/10.1093/nar/gkad736

“Synthetic Biology’s Promise and Peril: Shaping the Future of Medicine

Biology, Science / By Ruby Hyland

Image Credit: https://www.technologynetworks.com/drug-discovery/blog/how-is-synthetic-biology-shaping-the-future-of-drug-discovery-340290

As a recent and ever-changing form of medicine and science, synthetic biology is paving the way for the future of medicine. Defined as a “research and engineering domain of biology where a human-designed genetic program is synthesized and transplanted into a relevant cell type from an extant organism” (A.M. Calladine, R. ter Meulen, 2013), synthetic biology offers possible solutions to some of society’s most pressing medical issues. Through DNA sequence modification and genome editing, scientists have been able to edit genetic material in living organisms with tools such as CRISPR (Clustered regularly interspaced short palindromic repeats). This ability allows scientists to provide organisms with genetic tools that nature has not yet apportioned. CRISPR also allows for the creation of ‘living therapeutics’ and introduction of immunity cells into the human body.

So, what does this all mean? Well, synthetically creating genetic tools has already allowed for a breakthrough in different areas of production, such as the ability for silkworms to produce spider silk, as well as genetically engineered food, such as cheese, plant-based meat, etc., some of which are already available on a market scale. This provides society with a more sustainable way of creating different materials, which may be necessary as we continue to experience the impacts of consumerism on our planet’s environment. Living therapeutics and immune cells can help treat patients with various diseases, including multiple forms of cancer, providing them with a better chance of recovery and survival. Synthetic biology also assisted in the mass production of certain COVID-19 vaccines by manufacturing the SARS-CoV-2 genome sequence.

It’s clear that an abundance of benefits derive from the usage of synthetic biology. Consequently, as with most technological advancements, there is also a profusion of risks. A majority of these risks appear to be ethical and extremely dangerous. According to The University of Oxford, synthetic biology, although promising, gives biologists a concerning way of ‘playing god.’ Misusing synthetic biology could potentially destroy existing ecosystems and undermine our crucial distinction between living organisms and machines. The loss of this distinction could be catastrophic for humans’ view on the importance of different organisms and creates an ethical concern of prioritizing machines and technology over nature and living organisms. Synthetic biology also introduces the risk of the synthesization of known human pathogens, such as Influenza or Smallpox, which could be released in much more dangerous forms than what they currently are. Although some of these associated risks are unlikely, the potential danger they inflict could be devastating.

When considering the sad reality of human greed, it is essential to question whether the findings of synthetic biology will continue to be used for good. If put into the wrong hands, the technology could cause the decimation of multiple existing species, ultimately jeopardizing the balance of our ecosystem. Synthetic biology also poses the genuine risk of bioterrorism, as creating hazardous and genetically mutated organisms could be maliciously and violently released. Control of this technology is seen more in richer first-world countries, creating an inequality regarding access and usage. This gives certain countries, such as the U.S., an extensive scientific advantage over other countries, which could be used at the expense of other nations.

It is still being determined what the future of synthetic biology holds, but it is imperative that both the benefits and drawbacks are considered. Naturally, we hope synthetic biology continues to be used for the greater of humankind, but that could very easily and swiftly change. Therefore, and when considering that we are already in the midst of multiple ethical, moral, and environmental crises, it is necessary to be aware of the information we consume and promote, specifically regarding the ongoing evolution of technology and science.