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Category: genetics

Two-step approach creates more sustainable protein nanostructures for advanced sensing and therapeutics

Gas vesicles are among the largest known protein nanostructures produced and assembled inside microbial cells. These hollow, air-filled cylindrical nanostructures found in certain aquatic microbes have drawn increasing interest from scientists due to their potential for practical applications, including as part of novel diagnostic and therapeutic tools. However, producing gas vesicles is a difficult task for cells in the lab, hindering the development of applications.

In a study recently published in Nature Communications, a team of researchers led by Rice University bioengineer George Lu reports the development of a new genetic regulatory system to improve cell viability during the production of gas vesicles.

“In the past few years, studies have shown that gas vesicles’ ability to reflect sound makes them useful as unique and versatile acoustic reporter systems for biomedical research and clinical applications,” said Lu, an assistant professor in the Department of Bioengineering at Rice’s George R. Brown School of Engineering and Computing.

Epistasis study uncovers genetic interactions linked to heart disease

Euan Ashley’s lab explores the intricate interactions of gene variants. Tiny “typos,” or genetic mutations, can sneak into segments of DNA. Many of these are harmless, but some can cause health problems. Two or more genes can team up and change the outcome of a physical or molecular trait. This phenomenon, known as epistasis, occurs through complex interactions between genes that are functionally related—such as those that support protein creation.

Identifying these group dynamics provides crucial clues to how genetic diseases manifest and should be treated. But they’re not easily detected and often fly under the radar.

To help root out these connections, Ashley, MB ChB, DPhil, professor of genetics and of biomedical data science, and a team of scientists, including co-corresponding author Bin Yu, Ph.D., a professor of statistics and of electrical engineering and computer sciences at the University of California, Berkeley, have developed computational techniques to identify and understand the hidden ways epistasis influences inherited diseases.

The contribution of the membrane-bound complement regulatory proteins CD46 and CD55 in phases of acute lymphocytic leukemia and acute myelogenous leukemia

As for decay accelerating factor (DAF); also known as CD55, it is a type I cell surface protein that forms a single chain anchored to the membrane by glycosylphosphatidylinositol (GPI). It binds C3b and C4b inhibiting thereby the formation of C3 convertase and decreasing its half-life, thus providing a protective barrier threshold for plasma membranes of normal autologous cells against complement deposition and activation9,10.

The role of the complement system in cancer is complicated and has been debated for long. Malignant transformation is generally accompanied by genetic and epigenetic modifications which drastically alter patterns of glycosylation, cell-surface proteins and phospholipids11. These alterations can be identified by innate and adaptive immune mechanisms that guard the host against cancer development12. This is the known basis of the immune surveillance hypothesis. There is no direct evidence to support the argument that complement is able to eradicate emerging tumors. Nevertheless, taking into consideration that complement is intended for the recognition of non-self-elements, it is assumed that alterations in the tumor cell membranes’ composition render these cells as targets for complement recognition13. However, the relationship between inflammation and cancer is complicated and subject to contradictory forces14. Therefore, while acute responses are considered a vital part of the defense against cancerous cells, continuous inflammation in the tumor microenvironment increases the threat of neoplastic transformation and has several tumor-promoting effects15.

The current study aims at investigating the expression levels of mCRPs; CD46 and CD55 in the acute lymphocytic leukemia and acute myelogenous leukemia and to further elucidate its role in Egyptian cancer patients. To the best of our knowledge this study is one of very few studies tackling the complicated role of the complement system in acute leukemia.

EGFR activation sensitizes trigeminal NMDA receptors to promote pain and morphine analgesic tolerance in oral cancer

Oral squamous cell carcinoma (OSCC) is a painful disease that severely impairs eating, drinking, and talking (1–5). Patients with OSCC are less opioid responsive and develop opioid tolerance quicker than patients with other chronic pain conditions (6, 7). Escalating doses of opioids are required as tolerance develops, causing not only severe adverse effects (6) such as addiction but also prolonged hospitalizations and increased readmission rate in patients (8). The mechanisms underlying oral cancer pain and opioid tolerance are not well understood.

Epidermal growth factor receptor (EGFR) is a member of the receptor tyrosine kinases (RTKs) subfamily named HER/ERBB that is aberrantly expressed in 80 to 100% of the OSCC cases (9–11). EGFR antagonism including antibodies and tyrosine kinase inhibitors (TKIs) are US Food and Drug Administration (FDA) approved to treat many cancers, including OSCC (12–14). Clinical studies report pain relief in patients with neuropathic pain, including those associated with cancer after treatment with EGFR inhibitors (15, 16). Human genetic studies find associations between painful disease conditions and EGFR and its ligands, such as epiregulin, heparin-binding EGF (HB-EGF), and transforming growth factor–α (TGFα) (17–19). In animal models, HB-EGF directly causes dorsal root ganglion (DRG) cell excitation and elicits pain-like behaviors, whereas epiregulin mainly works in conjunction with underlying inflammation or tissue injury to generate pain (17, 19, 20). EGFR has also been implicated in opioid tolerance in human (21) and animal studies (20, 22, 23). Although elegant mechanistic studies suggest that EGFR can activate various pathways—through the ion channel transient receptor potential vanilloid 1 (TRPV1), the kinase cascade phosphatidylinositol 3-kinase (PI3K)–AKT–mammalian target of rapamycin (mTOR), the protease matrix metalloproteinase–9 (MMP-9), or the oncogene KRAS [to tetrahydrobiopterin (BH4)]—to increase pain sensitivities in mice (17, 24), these studies were done at the spinal level of noncancer pain models. It has been shown that EGFR involvement in pain is ligand and disease dependent (17, 25, 26), which warrants the investigation of EGFR signaling both in the setting of oral cancer pain that involves the trigeminal system and in opioid analgesic tolerance.

In this study, we aimed to determine how EGFR signaling contributes to oral cancer pain and opioid tolerance. We found that EGFR activation sensitizes trigeminal ganglion (TG) neurons and enhances glutamate N-methyl-d-aspartate receptor (NMDAR) signaling, resulting in heightened cancer pain and diminished opioid analgesic efficacy. EGFR ligands abundant in the OSCC tumor microenvironment trigger calcium influx, NMDAR phosphorylation, and protein kinase C (PKC) up-regulation in TG neurons. Last, we showed that EGFR activation induces presynaptic and postsynaptic hypersensitivity of NMDARs in the trigeminal nucleus caudalis (TNc) of the brainstem. Together, these findings establish EGFR-mediated NMDAR sensitization as a central mechanism underlying oral cancer pain and opioid tolerance and highlight EGFR as a promising therapeutic target.

Higher Prevalence of Coronary Microvascular Dysfunction in Patients With HFpEF Without Obesity

Advanced psc-based strategies for leukodystrophy therapy👇

✅Pluripotent stem cell (PSC)–based technologies are opening new avenues for the treatment of leukodystrophies by combining cell replacement, gene correction, disease modeling, and drug discovery within a unified framework.

✅One major approach focuses on the development of off-the-shelf PSC-derived neural progenitor cells (NPCs). By precisely editing immune-related genes, PSCs can be engineered to evade immune rejection. Strategies include knocking out core components of HLA class I and II pathways while introducing protective molecules such as HLA-E, or selectively removing highly immunogenic HLA alleles. These modifications allow the generation of universal donor NPCs that are resistant to T cell– and NK cell–mediated killing.

✅Autologous induced pluripotent stem cell (iPSC) therapy represents a personalized treatment strategy. Patient-derived somatic cells are reprogrammed into iPSCs, followed by genetic correction of disease-causing mutations using viral vectors or CRISPR/Cas9-based editing. Corrected iPSCs are then differentiated into neural stem cells (NSCs), NPCs, or oligodendrocyte progenitor cells (OPCs) and transplanted back into the same patient, minimizing immune complications.

✅Beyond therapy, iPSC-based disease models provide powerful tools to study leukodystrophy pathogenesis. Disease-specific iPSCs recapitulate key cellular phenotypes such as impaired differentiation, lysosomal dysfunction, oxidative stress, and apoptosis. These models enable direct investigation of early developmental defects that are difficult to access in patients.

✅Corrected iPSCs restore normal cellular phenotypes, allowing direct comparison between diseased and healthy isogenic cells. This approach clarifies causal mechanisms and validates gene correction strategies at the cellular level, supporting precision medicine.

✅iPSC-derived neural systems also support advanced drug discovery platforms. By generating complex neural cultures or myelinating organoids (“myelinoids”), researchers can model neuron–glia interactions and myelination in vitro. Coupled with immunofluorescence, transcriptomics, and high-throughput screening, these systems enable systematic identification of small molecules that promote myelination or correct metabolic defects.

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Scientists discover how to reactivate cancer’s molecular “kill switch”

(Farmington, Conn. – March 13, 2025) – Alternative RNA splicing is like a movie editor cutting and rearranging scenes from the same footage to create different versions of a film. By selecting which scenes to keep and which to leave out, the editor can produce a drama, a comedy, or even a thriller—all from the same raw material. Similarly, cells splice RNA in different ways to produce a variety of proteins from a single gene, fine-tuning their function based on need. However, when cancer rewrites the script, this process goes awry, fueling tumor growth and survival.

In a recent study reported in the Feb. 15 issue of Nature Communications, scientists from The Jackson Laboratory (JAX) and UConn Health not only show how cancer hijacks this tightly regulated splicing and rearranging of RNA but also introduce a potential therapeutic strategy that could slow or even shrink aggressive and hard-to-treat tumors. This discovery could transform how we treat aggressive cancers like triple-negative breast cancer and certain brain tumors, where current treatment options are limited.

At the heart of this work, led by Olga Anczuków, an associate professor at JAX and co-program leader at the NCI-designated JAX Cancer Center, are tiny genetic elements called poison exons, nature’s own “off switch” for protein production. When these exons are included in an RNA message, they trigger its destruction before a protein can be made—preventing harmful cellular activity. In healthy cells, poison exons regulate the levels of key proteins, keeping the genetic machinery in check. But in cancer, this safety mechanism often fails.

Genetic identification of mouse trigeminal afferents responsible for mechanical allodynia

Peripheral mechanisms by which the nerve afferents send signals after nerve injury in mechanical C is not well understood.

The researchers identify a subset of trigeminal afferents in mice activated by facial brushing after nerve injury. Many of brushing-activated (BA) trigeminal ganglia (TG) neurons express neurofilament200 and Ntrk3, markers for low-threshold mechanoreceptors, with lower co-localization with nociceptor markers such as Calca or Trpv1.

Inhibition of BA TG neurons reduces mechanical allodynia, while their activation increases spontaneous face wiping after nerve injury.

Knockdown of Piezo2 from BA TG afferents reduces mechanical allodynia. Thus, targeted manipulations reveal these neurons’ causal role in pain-like behaviors and heightened sensitivity, providing new insights into primary afferents underlying mechanical allodynia. sciencenewshighlights ScienceMission https://sciencemission.com/trigeminal-afferents

Peripheral mechanisms of mechanical allodynia after nerve injury remain unclear. Li et al. identify a subset of trigeminal afferents in mice activated by facial brushing after nerve injury. Targeted manipulations reveal these neurons’ causal role in pain-like behaviors and heightened sensitivity, providing new insights into primary afferents underlying mechanical allodynia.

Uncovering genetic interactions in the DNA repair network in response to endogenous damage and ionizing radiation

Nebenfuehr et al. perform a combinatorial CRISPR-Cas9 screen targeting 461 DNA damage response genes under basal and irradiated conditions. The study maps thousands of genetic interactions, generating a rich resource to uncover mechanisms of genome maintenance and inspire future studies.

Dr. Chris Oswald — Precision Nutrition, Epigenetics & Practitioner-Led Longevity Care

Precision Nutrition, Epigenetics & Practitioner-Led Longevity Care — Dr. Chris Oswald — Head of Medical Affairs, Pure Encapsulations, Nestlé Health Science.

Dr. Chris Oswald, DC, CNS, is Head of Medical Affairs for Pure Encapsulations (https://www.pureencapsulations.com/), part of Nestlé Health Science family. He is a chiropractor, certified nutrition specialist and certified functional medicine practitioner and has been treating patients since 2007.

At Pure Encapsulations, Dr. Oswald leads medical education, scientific strategy, and innovation across well-known professional brands including Pure Encapsulations, Douglas Labs, Klean Athlete, Genestra, and others. In this role, he sits at the intersection of clinical science, practitioner education, and product innovation — translating complex evidence into practical tools that help healthcare professionals practice more confident, personalized nutritional medicine.

Dr. Oswald’s clinical work, in combination with his work in professional dietary supplement companies, gives him unique insight into the creation of clinically useful tools and education to support the unique needs of clinicians and patients in functional, integrative and natural health.

Before joining Pure Encapsulations, Dr. Oswald held senior leadership roles across the nutraceutical and health tech landscape, including Chief Science Officer, Head of Product Innovation and R&D, Head of Operations, Interim Head of Sales, and VP of Nutraceuticals at companies like January AI and Further Food. Across those roles, he’s led everything from supply chain and regulatory strategy to product development, claims substantiation, and national practitioner education.

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