Cohesin, a protein complex that forms loops in the human genome, plays a crucial role in determining the architecture of our genetic material and regulating gene expression. However, its function and behavior have remained somewhat mysterious until now.

Researcher Professor Eva Estébanez-Perpiñá from the University of Barcelona, along with her team and international collaborators, has made significant strides in understanding how cohesin works. Their study, published in Nucleic Acids Research, sheds light on the protein’s interaction with chromatin structure and its role in altering gene expression.

Cohesin consists of four subunits: SMC1, SMC3, SCC1/RAD21, and STAG (also known as SA or SCC2). Previous studies had identified 25 proteins that regulate these subunits and their biological function. Estébanez-Perpiñá’s team has now discovered how the NIPBL protein interacts with both MAU2 and the glucocorticoid receptor (GR), a transcription factor essential for cellular functions.

This ternary complex, comprising NIPBL, MAU2, and GR, modulates transcription by facilitating the interaction of GR with these two proteins. When GR interacts with NIPBL and MAU2, it alters chromatin structure and affects gene expression. This discovery has significant implications for understanding Cornelia de Lange syndrome, a rare disease caused by mutations in genes involved in cohesin formation.

The researchers used advanced microscopic techniques to visualize real-time molecular complexes binding to chromatin, as well as biochemical and biophysical methods to analyze the complex from different structural and cellular perspectives.

Their findings not only improve our comprehension of cohesin’s role but also highlight its potential involvement in other diseases, such as asthma and autoimmune pathologies. As research continues, scientists will likely uncover more about this enigmatic protein and its intricate relationships with chromatin structure and gene expression.

A groundbreaking study has shed new light on the fundamental mechanisms governing microtubule growth within cells. Researchers from Queen Mary University of London and the University of Dundee have made a significant breakthrough by discovering that the ability of tubulin proteins at microtubule ends to connect with each other sideways determines whether a microtubule elongates or shortens.

Microtubules are crucial protein structures that form the internal skeleton of cells, providing structural support and generating dynamic forces that push and pull. These tiny filaments constantly assemble and disassemble by adding or removing tubulin building blocks at their ends. However, the precise rules dictating whether a microtubule grows or shrinks have long remained a mystery due to the complexity and miniature size of their ends.

The collaborative research team has cracked part of this code using advanced computer simulations coupled with innovative imaging techniques. This interdisciplinary approach has allowed them to address this complex biological question from a fresh perspective, bridging physics and biology.

Dr. Vladimir Volkov, co-lead author from Queen Mary University of London, explained the significance of their findings: “Understanding how microtubules grow and shorten is very important – this mechanism underlies division and motility of all our cells. Our results will inform future biomedical research, particularly in areas related to cell growth and cancer.”

Dr. Maxim Igaev, co-lead author from the University of Dundee, highlighted the power of their interdisciplinary approach: “Bridging physics and biology has allowed us to address this complex biological question from a fresh perspective. This synergy not only enriches both fields but also paves the way for discoveries that neither discipline could achieve in isolation.”

This exciting research deepens our understanding of fundamental cellular processes and opens potential new avenues for biomedical research, particularly in areas concerning cell proliferation and the development of treatments for diseases like cancer.

Breaking Ground in Cancer Treatment: Innovative Immunotherapy Shows Promise Against Aggressive Blood Cancers

A groundbreaking type of immunotherapy has shown promising results in treating aggressive blood cancers, according to a recent international phase 1/2 clinical trial. The innovative CAR-T cell therapy was specifically designed to target cancerous T cells and achieved complete remission in a significant number of patients who had run out of treatment options.

The study, led by researchers at Washington University School of Medicine in St. Louis, evaluated the safety and efficacy of an off-the-shelf CAR-T cell immunotherapy that targets aggressive blood cancers, including T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma. The clinical trial included 28 adult and adolescent patients who had been diagnosed with these rare and aggressive cancers.

The results were published in the journal Blood and showed that most of the patients who received the full dose of CAR-T cells achieved complete remission, with an overall response rate of 91%. Eight out of 11 patients (72.7%) achieved complete remission, and six patients remained in remission at the study’s data cut-off.

The therapy, called WU-CART-007, was developed by Wugen, a WashU biotech startup company founded by researchers from Washington University School of Medicine. The clinical trial was conducted across multiple sites worldwide, including Australia, Europe, and various locations in the United States.

“This has the potential to become a transformative advance in the field,” said senior author John F. DiPersio, MD, PhD, the Virginia E. & Sam J. Golman Professor of Medicine at WashU Medicine. “The trial demonstrated a high likelihood of response to the therapy and even remission. This CAR-T cell treatment shows promise in becoming a ‘bridge-to-transplant’ therapy for patients who would otherwise not be eligible for stem cell transplantation.”

While larger studies are necessary before the researchers can determine whether this new therapy could be curative on its own, the results are promising and offer hope for those affected by these aggressive blood cancers.

Innovative CAR-T Cell Therapy

The CAR-T cell therapy evaluated in the trial is considered a “universal” therapy because it harnesses CRISPR gene editing technology to produce cells from healthy donors that can be used to treat patients with T-cell cancers. This approach eliminates the need for personalized therapies, which must be adapted from each patient’s immune cells.

Using CRISPR gene editing tools, the production process deletes the T cell receptor from the donor cells, reducing the risk of graft-versus-host disease and preventing CAR-T cell fratricide, where therapeutic T cells attack healthy tissue. The modified CAR-T cells are engineered to target a protein called CD7 on the surface of cancerous T cells to then destroy the cancer.

A larger international clinical trial is already underway, and researchers hope that this universal CAR-T cell therapy can become an approved treatment for patients with deadly T-cell cancers.