Finding Inspiration for Drug Development in Metabolic Regulators

The metabolic pathways that shape how our bodies use nutrients and energy are under constant adjustment, with metabolites pay a key role in managing their function and activity. There are thousands of metabolites inside our cells, and surprisingly little is known about how most of them interact with other cellular components, even though when these interactions with proteins are disrupted, it can leave us more vulnerable to disease. Continue reading → Finding Inspiration for Drug Development in Metabolic Regulators

Transferred Mitochondria Accumulate Reactive Oxygen Species, Promoting Proliferation

Cancer cells don’t act on their own. Their behavior is influenced by neighboring cells, which sometimes help them grow and spread. For instance, immune cells called macrophages patrol the body, engulfing and destroying potential threats. But when they interact with tumors, they can often produce signals that drive the disease. Continue reading → Transferred Mitochondria Accumulate Reactive Oxygen Species, Promoting Proliferation

A Protein that Blocks Virus Budding

A collaboration between the labs of University of Utah Health researchers Nels Elde, PhD, and Wesley Sundquist, PhD, showed that some mammals contain duplicated and shortened genes for a key ESCRT protein. The resulting “retroCHMP3” proteins block the release of HIV and other enveloped viruses. Continue reading → A Protein that Blocks Virus Budding

A Cellular Structure that Protects Against Amino Acid Stress

Amino acids form the basic building blocks of all life, used by cells both as fuel and in building proteins and other complex molecules. Cellular amino acid levels must be tightly controlled. Amino acid surplus is problematic and is a characteristic of many age-related diseases, including cancer and diabetes. Scientists do not yet fully understand how cells detect and respond to amino acid excess, and how this excess causes cellular damage. Continue reading → A Cellular Structure that Protects Against Amino Acid Stress

Reconstituting HIV Replication in a Test Tube

Reverse transcription and integration are key events in retrovirus replication and are also targets of successful anti-HIV therapies. Reverse transcription creates a double-stranded DNA copy of the viral RNA genome, and integration archives that copy within the genome of the infected cell. However, studies of the mechanisms underlying these steps of the viral life cycle remain challenging because these processes are performed by viral core particles located deep within the infected cell cytoplasm and nucleus. Continue reading → Reconstituting HIV Replication in a Test Tube

Visualizing the SARS-CoV-2 Life Cycle

SARS-CoV-2 is defining disease of the current era. Many biological researchers have redirected their focus to understanding and defeating the virus, rapidly leading to new insights into how the virus gains access to and hijacks human cells. University of Utah Health investigator Janet Iwasa, PhD, and colleagues have used this information to create detailed molecular animations of different stages of the SARS-CoV-2 life cycle. Continue reading → Visualizing the SARS-CoV-2 Life Cycle

A Potent, Long-lasting HIV Capsid Inhibitor

Reverse transcription and integration are key events in retrovirus replication and are also targets of successful anti-HIV therapies. Reverse transcription creates a double-stranded DNA copy of the viral RNA genome, and integration archives that copy within the genome of the infected cell. However, studies of the mechanisms underlying these steps of the viral life cycle remain challenging because these processes are performed by viral core particles located deep within the infected cell cytoplasm and nucleus. Continue reading → A Potent, Long-lasting HIV Capsid Inhibitor

How Cells Choose to Create Energy

To supply their energy needs, cells typically choose between utilizing glucose in the cytoplasm (aerobic glycolysis and lactic acid fermentation) or “burning” pyruvate in the mitochondria (mitochondrial carbohydrate oxidation). Although this is arguably the most fundamental metabolic decision that cells make, before 2012 it was not clear how cells import pyruvate into mitochondria to fuel ATP production. Continue reading → How Cells Choose to Create Energy

Structures and Mechanisms of Protein Remodeling Machines

When a cellular protein has done its job or lost its utility, it should be removed, recycled, or remodeled. These tasks are performed by members of the ubiquitous family of AAA ATPases (ATPases associated with diverse cellular activities) that convert the energy of ATP hydrolysis into mechanical forces that can unfold protein aggregates, degrade unwanted proteins, and remodel protein complexes. Continue reading → Structures and Mechanisms of Protein Remodeling Machines

Fast-acting Insulins from Cone Snails

Faster acting human insulins are needed to improve the efficacy of diabetic insulin pumps. Over the past few years, collaborating teams led by Olivera, Safavi-Hemami, Schlegel, Yandell, and Chou have made the remarkable discovery that fish-hunting cone snails use fast-acting insulins to inactivate their prey by inducing hypoglycemia. Continue reading → Fast-acting Insulins from Cone Snails

Sensing and Regulating Cellular Energy Production

Cells must decide when to expand mitochondrial capacity to accommodate increased energy demands. Rutter, Winge, and colleagues have shown that the ancient mitochondrial fatty acid synthesis system has a profound and unexpected regulatory role in driving mitochondrial biogenesis. Continue reading → Sensing and Regulating Cellular Energy Production

Structure and Function of the Polycystic Kidney Disease Channel

The kidney senses and responds to physiological changes, such as pH, ionic strength, pressure, and nutrient levels. Sensing is mediated by a coupled sensor/ion channel complex called the Polycystic Kidney Disease Channel, which is composed of two subunits, the PKD1 (the primary sensor) and PKD2 (the channel). Continue reading → Structure and Function of the Polycystic Kidney Disease Channel

Identifying RNAs from Invading Viruses

Biochemical and structural studies from Bass, Shen, Iwasa, and colleagues revealed how Dicer-2, an RNA processing, and antiviral defense enzyme, distinguishes and differentially processes double-stranded RNA (dsRNA) substrates by sensing the unique chemistry at their termini. Continue reading → Identifying RNAs from Invading Viruses

Viral RNA Modulation of Host Gene Expression

Viruses depend on and modulate their hosts’ cellular environments to maximize replication. Cazalla and colleagues studied the small RNAs from H. saimiri, a herpesvirus that establishes latency in the T cells of New World primates and can cause aggressive leukemias and lymphomas in non-natural hosts. Continue reading → Viral RNA Modulation of Host Gene Expression

Cellular Membrane Remodeling

Cells are continually severing, fusing, and reshaping their membranes. One of the essential cellular membrane remodeling systems is the ESCRT (Endosomal Sorting Complexes Required for Transport) pathway, whose cellular functions include endosomal membrane remodeling, membrane repair, enveloped virus budding, closure of the nuclear envelope, and cytokinetic abscission. Continue reading → Cellular Membrane Remodeling