Can AI Replace High-Throughput Screens for Drug Discovery?

This image was created with the assistance of AI

For decades, pharmaceutical companies have relied on high-throughput screening (HTS) as the first step in the drug discovery process. After an initial screening of thousands of compounds, scientists select a smaller list of candidate drugs that is then used for further downstream testing. A major limitation to HTS, however, is the need to synthesize all compounds used in the screen—the compounds need to physically exist to be tested. This significantly limits the number of compounds that can be tested, hindering the discovery of new drugs.

What if we could test compounds even before they are synthesized?

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How Avian Influenza Crosses Species

Avian influenza, commonly known as bird flu, has become an increasingly severe public health issue. According to the CDC, the frequency of avian influenza outbreaks and diversity of virus subtypes have increased significantly in the past decade. In 2022, there were reports of sporadic H5 virus infections in mammals across several U.S. states, Canada, and other countries. Affected animals included fox kits, bobcats, coyote pups, raccoons, skunks, mink, and even seals. Human cases of H5N6 and other subtypes following poultry exposures were reported in China, with several cases resulting in severe or critical illness and death.

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Macrophages: The Unsung Heroes of Immune Response and Biologic Drug Development 

When we think about the immune system, B cells and T cells are often the focus of attention. B cells are known for producing antibodies, and T cells are celebrated for their cytotoxic capabilities. More recently, however, macrophages are being brought into the spotlight and recognized for their integral role in immune defense and the field of biologic drug development. 

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Treating Solid Tumors: Combining CAR-T Cell Therapy with Probiotics

Chimeric Antigen Recepter (CAR)-T cell therapy is a personalized immunotherapy that harnesses the patient’s own immune system to combat cancer. It is done by engineering the patient’s T cells to specifically target and attack cancer cells in their body, and it has shown great success in treating various blood cancers such as leukemia.

Treating solid tumors with CAR-T cells, however, has proved much more challenging. This is mainly because solid tumors contain a heterogeneous population of cells, expressing a variety of antigens—many of which are also expressed in healthy cells. Therefore, T cells targeting solid tumors could potentially attack healthy tissue, resulting in serious side effects. In addition, solid tumors create a hostile microenvironment that is difficult for CAR-T cells to infiltrate.

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Studying the Genetic Basis of Type 2 Diabetes with An Automated Maxwell® Workflow

Blood collection tubes in a rack. Researchers are learning more about  Type 2 diabetes

Over the past few decades, the prevalence of diabetes has been on the rise. According to the WHO, 422 million people worldwide have diabetes, causing an estimated 1.5 million deaths every year. Among those with diabetes, 95% have type 2 diabetes—which is caused by the body’s resistance to insulin. It is known that risk factors for type 2 diabetes include older age, excess weight, poor diet and family history. However, the precise genetic basis of type 2 diabetes is still largely a mystery.

Dr. Mark McCarthy’s lab at the Oxford Center for Diabetes, Endocrinology and Metabolism (OCDEM) focuses on understanding the genetic causes of type 2 diabetes. Identifying which genes contribute to type 2 diabetes could provide opportunities for developing new therapeutics. Chris Grove, former lab manager in Dr. McCarthy’s lab, explained how they have approached this challenge.

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MISpheroID: A Knowledgebase to Improve Reproducibility in Spheroid Research

Spheroid research is  now a common component of cell biology and drug discovery science

Advantages of Spheroids

In the past decade, there has been a sharp rise in studies using spheroids as cell models for basic research and drug discovery. Spheroids are self-organized aggregation of cells that form a spherical mass, and they have become widely popular because they are much more physiologically relevant compared to flat 2D cell cultures.

In spheroids, the inner cells have less access to nutrients and oxygen compared to the outer layer, forming a natural gradient. As a result, metabolite concentration and cellular state such as proliferation and differentiation, can be very different at the periphery compared to the inner core. This phenomenon, known as “heterogeneity”, makes 3D tumor spheroids much more representative of actual tumors in the human body.

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How to Get Real-Time Kinetic Data With GloMax® Microplate Readers

Understanding how a compound or drug affects cellular pathways often requires measuring kinetic changes over an extended period of time—from several hours to days. Live-cell kinetic cell-based assays that measure cell viability, cytotoxicity, apoptosis and other cellular pathways are great for collecting real-time data. You don’t necessarily need expensive equipment to run these types of assays. In the videos below, Dr. Sarah Mahan, a research scientist at Promega, demonstrates how you can easily get great 24-hour or multi-day kinetic data using a GloMax® Microplate Reader.

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How A New Wastewater Surveillance Method Predicted COVID-19 Cases in Italy

Wastewater-based epidemiology (WBE), or sewershed surveillance, is the analysis of wastewater to identify the presence of biologicals or chemicals for the purpose of monitoring public health. In the past, WBE has been used to detect the presence of pharmaceutical or industrial waste, drugs and viruses. Now, it is seen as a valuable tool to monitor COVID-19 outbreaks.

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Rare Human Antibody Could Lead to A Universal Coronavirus Vaccine

Artists 3D rendering of SARS-CoV-2. One lab group is trying to develop a universal coronavirus vaccine.

As we’ve all learned from the current global COVID-19 pandemic, coronaviruses are generally bad news. Among the four genera of coronaviruses, the betacoronavirus genus has been especially notorious. In the past 20 years, three highly pathogenic betacoronaviruses, MERS-CoV, SARS-CoV and SARS-CoV-2 have resulted in serious pandemics. All three of these viruses originated from bats, highlighting the continued risk of coronavirus transmission from animals to humans.

Typically, when a new viral threat emerges, researchers scramble to develop drugs or vaccines after the virus has already gotten out of control. However, developing a vaccine for each new virus is a slow and painstaking process, and many lives will be lost before a vaccine is distributed. But what if we had one, universal coronavirus vaccine that could neutralize not only all existing betacoronaviruses, but any new variants that emerge in the future?

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New Therapy for Brain Tumors: High-Pressure Oxygen Rewires Glucose Metabolism in Glioblastoma

Glioblastoma (GBM) is an aggressive type of brain tumor, and one of the deadliest cancers. GBM is often treated with surgery, radiation and chemotherapy, but even if the initial treatment is successful, a majority of patients relapse within months. One reason why GBM is so difficult to treat is the hypoxic (low-oxygen) tumor environment. It is known that hypoxic cells are resistant to radiotherapy; the greater the number of tumor stem cells in a hypoxic environment, the less efficient radiotherapy is at controlling tumor growth.

A new therapeutic approach aims to remove the hypoxic environment in GBM by administering pure oxygen to patients at high pressure, known as “hyperbaric oxygen (HBO) therapy”. Previous studies have shown that HBO improves the efficacy of radiotherapy in GBM patients. However, the therapeutic mechanism of HBO was largely unknown. That is, until now.

Dr. Anna Tesei, the Head of Radiobiomics and Drug Discovery at the Biosciences Laboratory of IRST-IRCCS in Italy, recently published a study on the mechanism in which HBOT affects GBM tumor cells and the tumor environment. “The main purpose of our study was to provide a preclinical rationale for the use of hyperbaric oxygen in association with radiotherapy for the treatment of GBM,” she says.

Dr. Anna Tesei is studing glucose metabolism in glioblastoma cells.
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