Lifeboat Foundation

Researchers at the National Institutes of Health (NIH) and their collaborators have discovered a new way in which RAS genes, which are commonly mutated in cancer, may drive tumor growth beyond their well-known role in signaling at the cell surface.

Mutant RAS, they found, helps to kick off a series of events involving the transport of specific nuclear proteins that lead to uncontrolled tumor growth, according to a study published November 11, 2024, in Nature Cancer.

RAS genes are the second most frequently mutated genes in cancer, and mutant RAS proteins are key drivers of some of the deadliest cancers, including nearly all pancreatic cancers, half of colorectal cancers, and one-third of lung cancers.

Microorganisms—bacteria, viruses and other tiny life forms—may drive biological variation in visible life as much, if not more, than genetic mutations, creating new lineages and even new species of animals and plants, according to Seth Bordenstein, director of Penn State’s One Health Microbiome Center, professor of biology and entomology, and the Dorothy Foehr Huck and J. Lloyd Huck Endowed Chair in Microbiome Sciences.

Bordenstein and 21 other scientists from around the world published a paper in Science, summarizing research that they said drives a deeper understanding of biological variation by uniting life’s seen and unseen realms.

Continue reading “Q&A: Holobiont biology, a new concept for exploring how microbiome shapes evolution of visible life” »

Evo is a large language model that is not trained on words but on the genomes of millions of microbes. It can accurately predict the effects of mutations.

To determine the type and severity of a cancer, pathologists typically analyze thin slices of a tumor biopsy under a microscope. But to figure out what genomic changes are driving the tumor’s growth—information that can guide how it is treated—scientists must perform genetic sequencing of the RNA isolated from the tumor, a process that can take weeks and costs thousands of dollars.

Now, Stanford Medicine researchers have developed an artificial intelligence-powered computational program that can predict the activity of thousands of genes within tumor cells based only on standard microscopy images of the biopsy.

The tool, described online in Nature Communications Nov. 14, was created using data from more than 7,000 diverse tumor samples. The team showed that it could use routinely collected biopsy images to predict genetic variations in breast cancers and to predict patient outcomes.

OneSkin, founded by Brazilian PhD scientists in 2016, reports that it has now closed a Series A funding round led by Selva Ventures, together with contributions from PLUS Capital, Unilever Ventures, Able Partners, SOSV, and Meta Planet. This brings the accumulated capital of the firm to 20 million US dollars.

The goal of the OneSkin team is the research and development of topical treatments that promote skin longevity. The brand’s efforts have led to the development of the peptide OS-01, which is claimed to reverse the aging of the skin by preventing the accumulation of “old”, non-dividing senescent cells, as well as shield skin cells from DNA damage. OS-01 is already available on the market in several different products offered by the company.

Senescent cells have been the focus of a significant amount of biogerontological research in recent years. Scientists claim that every cell in the human body has a limited capacity for division, governed by genetic factors. When the cells reach the point in their lifecycle where their ability to divide is permanently halted, they remain in a minimally-functional state in the tissue types they inhabit.

Skull bone marrow expands during adult life, exhibits lifelong vascular growth and increases its haematopoietic potential during ageing.

A new drug strategy that regulates the tumor immune microenvironment may transform a tumor that resists immunotherapy into a susceptible one, according to a study by researchers from the Johns Hopkins Kimmel Cancer Center and Oregon Health & Science University.

The immune microenvironment around a pancreatic tumor has suppressed immune activity, allowing the tumor to evade attacks by the immune system. The cancer evades the immune system by attracting suppressive cells into the tumor, which limits access of tumor-killing T cells. Because of that so-called immune desert environment, pancreatic ductal adenocarcinoma (PDA), the most common type of pancreatic cancer, has been resistant to immune-based therapies that have successfully treated a variety of other cancers, including melanoma and lung cancer.

In a phase 2 clinical trial, a research team led by Nilofer Azad, M.D., professor of oncology and co-leader of the Kimmel Cancer Center’s Cancer Genetics and Epigenetics Program, and Marina Baretti, M.D., the Jiasheng Chair in Hepato-Biliary Cancer at the Kimmel Cancer Center, tested the safety and efficacy of the combination of two drugs: an immunotherapy, nivolumab, and an epigenetic drug, entinostat — a histone deacetylase inhibitor (HDACi). The combination was studied in a group of 27 patients with advanced PDA who had previously been treated with chemotherapy.

As people who research aging like to quip, the best thing you can do to increase how long you live is to pick good parents. After all, it has long been recognized that longer-lived people tend to have longer-lived parents and grandparents, suggesting that genetics influence longevity.

Complicating the picture, however, is that we know that the sum of your lifestyle, specifically diet and exercise, also significantly influences your health into older age and how long you live. What contribution lifestyle versus genetics makes is an open question that a recent study in Nature has shed new light on.

Scientists have long known that reducing calorie intake can make animals live longer. In the 1930s, it was noted that rats fed reduced calories lived longer than rats who could eat as much as they wanted. Similarly, people who are more physically active tend to live longer. But specifically linking single genes to longevity was until recently a controversial one.

Microbial systems have been synthetically engineered to deploy therapeutic payloads in vivo.

To enable effective cancer vaccination, we developed an engineered bacterial system in probiotic Escherichia coli Nissle 1917 (EcN) to enhance expression, delivery and immune-targeting of arrays of tumour exonic mutation-derived epitopes highly expressed by tumour cells and predicted to bind major histocompatibility complex (MHC) class I and II (Fig. 1a). This system incorporates several key design elements that enhance therapeutic use: optimization of synthetic neoantigen construct form with removal of cryptic plasmids and deletion of Lon and OmpT proteases to increase neoantigen accumulation, increased susceptibility to phagocytosis for enhanced uptake by antigen-presenting cells (APCs) and presentation of MHC class II-restricted antigens, expression of listeriolysin O (LLO) to induce cytosolic entry for presentation of recombinant encoded neoantigens by MHC class I molecules and T helper 1 cell (T_H1)-type immunity and improved safety for systemic administration due to reduced survival in the blood and biofilm formation.

To assemble a repertoire of neoantigens, we conducted exome and transcriptome sequencing of subcutaneous CT26 tumours. Neoantigens were predicted from highly expressed tumour-specific mutations using established methods^14,15, with selection criteria inclusive of putative neoantigens across a spectrum of MHC affinity^16,17. Given the importance of both MHC class I and MHC class II binding epitopes in antitumour immunity^15,18,19, we integrated a measure of wild-type-to-mutant MHC affinity ratio—termed agretopicity^17,20—for both epitope types derived from a given mutation, to help estimate the ability of adaptive immunity to recognize a neoantigen. Predicted neoantigens were selected from the set of tumour-specific mutations satisfying all criteria, notably encompassing numerous recovered, previously validated CT26 neoantigens¹⁵ (Extended Data Fig. 1a).

Continue reading “Probiotic neoantigen delivery vectors for precision cancer immunotherapy” »