Bioblasts

Richard Altmann (1852-1900) was a German prosecutor-turned-anatomy professor who focused on advancing microscopy techniques in his day. Using a new staining technique, he observed filaments in nearly every cell type he viewed. These filaments developed from granules, which Altmann deduced were elementary living units.

He called them “bioblasts.”

His conclusions were not well-received by peers.

These days, it’s believed Altmann was describing mitochondria, a term coined by Carl Benda in 1898 replaced Altmann’s “bioblasts.” And no one disputes the significance of Altmann’s original observations.

Mitochondria  are cellular organelles that covert fuel into energy, the so-called “powerhouses of the cell.” They have many responsibilities and notably, possess their own genes apart from the cell’s nucleus. This fact supports the hypothesis that mitochondria were originally free-living prokaryotic cells lacking a nucleus that permanently fused with eukaryotic cells in the distant past.

Given their fundamental and expansive importance, mitochondria are the focus of much research. At Sanford Burnham Prebys, Peter Adams, PhD, with collaborators elsewhere, are  exploring the role they play in cellular aging and immune responses, and particularly how they may affect the connection between aging and liver cancer.

About the art: Odra Noel is a medical doctor and PhD in basic science, with additional degrees in aesthetics and music. Her silk paintings focus primarily on human biology, often informed by microscopy. Wellcome Collection.

T cell killing cancer cell

T cells are a type of white blood cell (lymphocytes) that develop from stem cells in bone marrow and are part of the adaptive immune system, which constantly monitors the body for threats. They help protect the body from infection and may help fight cancer. Each T cell is unique, designed to fight only one type of intruder.

 At Sanford Burnham Prebys, Linda Bradley, PhD, Jennifer Hope, PhD, and colleagues are working to help revive exhausted T cells to tackle immunotherapy-resistant cancers—a major emphasis in cancer research.

Meanwhile, Kelly Kersten, PhD, is studying how T cells fundamentally interact with cancer cells and the microenvironment, looking for ways to improve immunotherapies and reduce the likelihood of treatment resistance, which is common in many types of cancer.

About the art: Odra Noel is a medical doctor and PhD in basic science, with additional degrees in aesthetics and music. Her silk paintings focus primarily on human biology, often informed by microscopy. Wellcome Collection.

Cardiac muscle

Despite decades of research, heart disease is still the leading cause of death in the industrialized world. The human heart beats roughly 100,000 times a day pushing 2,000 gallons, or about five quarts a minute. Disorders that affect the abilities of cardiac muscle to beat normally are called cardiomyopathies. They can affect people of any age, race or sex, and are often inherited. Cardiomyopathy poses a significant health risk, leading to heart failure. More than half of all heart transplants are due to cardiomyopathies.

Among the most common of cardiomyopathies is atrial fibrillation or AFib, a form of cardiac arrhythmia in which the heart beats abnormally: usually too fast and irregularly. More than 5 million people in the U.S. have AFib, which in 2021 was cited in 232,030 death certificates and named as the underlying cause of death in 28,037. The risk of developing AFib is increased by congenital defects, heart attacks, high blood pressure, pneumonia, viral infections and sleep disorders. The biggest risk factor is age with roughly 10% of people over age 65 developing AFib. How genetics, age and other risk factors interact to cause AFib is unknown.

At Sanford Burnham Prebys, researchers are investigating the gene networks that result in AFib. Recently, Alexandre Colas, PhD, and Karen Ocorr, PhD, with colleagues elsewhere, published findings that describe a multi-model platform for identifying causative genes for AFib, a major step toward finding new treatments.

About the art: Odra Noel is a medical doctor and PhD in basic science, with additional degrees in aesthetics and music. Her silk paintings focus primarily on human biology, often informed by microscopy. Wellcome Collection.

Neurons

Neurons or nerve cells are the main components of nervous tissue in all animals except sponges and placozoans. Plants and fungi don’t have nerve cells. They are characterized by the ability to fire electric signals called action potentials across a neural network, either in the brain or through the central and peripheral nervous systems.

There are three basic types of neurons based on function. Sensory neurons respond to stimuli, such as touch, sound or light. They trigger messages to the spinal cord or brain. Motor neurons receive signals from the brain and spinal cord to control everything from muscle contractions to glandular output. Interneurons connect multiple neurons to create neural circuits.

There are approximately 100 billion neurons in a mature human brain. Each can make connections with more than 1,000 other neurons, creating approximately 60 trillion total neuronal connections.

Given their profound and fundamental importance to every aspect of life, the roles of neurons in both health and disease has long been a matter of intense study. At Sanford Burnham Prebys, that effort has often focused on the fate of neurons in neurodegenerative diseases like Alzheimer’s and in the processes of aging. By 2050, the number of Alzheimer’s patients age 65 and older may nearly triple from 5 million to 13.8 million.

Leading those investigations are researchers Jerold Chun, MD, PhD, Anne Bang, PhD and Timothy Huang, PhD.

About the art: Odra Noel is a medical doctor and PhD in basic science, with additional degrees in aesthetics and music. Her silk paintings focus primarily on human biology, often informed by microscopy. Wellcome Collection.

Golgi apparatus

The Golgi apparatus or complex, named after its discoverer Camillo Golgi, functions as a factory and distribution warehouse in which proteins received from the endoplasmic reticulum, part of a cells transportation system, are further processed and sorted for shipment to their eventual destinations.

The organelle looks like a set of stacked membranes. Here, incoming proteins might be paired with carbohydrates (a sort of sugar frosting) to create so-called glycoproteins, which serve many functions in the body, from providing structure (such as collagens) to acting as antibodies to hormonal activities.

The process of creating glycoproteins is called glycosylation. It’s an extraordinarily complex process involving more than 500 genes and when some are defective, a group of metabolic diseases called Congenital Disorders of Glycosylation (CDG) result. Roughly 200 types of CDG have been identified.

At Sanford Burnham Prebys, Hudson Freeze, PhD, specializes in CDGs as director of the Sanford Children’s Health Research Center. This large group of rare genetic disorders cause a wide array of health issues, mostly emerging in childhood, and often foretell an early death.

There are no known cures for CDGs, but clinical trials for novel therapies have been launched, providing real hope for better management of symptoms, improved quality of life and, ultimately, cures.

About the art: Odra Noel is a medical doctor and PhD in basic science, with additional degrees in aesthetics and music. Her silk paintings focus primarily on human biology, often informed by microscopy. Wellcome Collection.

Protein pore

Nuclear pores are protein-lined channels connecting the inner nucleus of a eukaryotic cell with the surrounding cytoplasm—the gelatinous liquid that fills the inside of the cell, giving it shape and protection.

Nuclear pores allows small molecules and ions to freely diffuse into or out of the nucleus, giving passage to critical information and materials for cell functions.

At Sanford Burnham Prebys, Maximiliano D’Angelo, PhD, and Valeria Guglielmi, PhD, are investigating how nuclear pores in cancer cells are different and how these differences contribute to malignancy and tumor development. By better understanding  the functions of nuclear pores in healthy and cancerous cells, they hope to develop novel therapies that target the development and progression of cancer at the cellular level.

About the art: Odra Noel is a medical doctor and PhD in basic science, with additional degrees in aesthetics and music. Her silk paintings focus primarily on human biology, often informed by microscopy. Wellcome Collection.

Cellular space

Human cells come in a variety of sizes, from 10 to 100 micrometers in diameter. (A micrometer or micron is 1,000 times smaller than a millimeter.) Imagine a single grain of salt cut into five pieces. Each of those pieces would be about the size of an average human cell, invisible without magnification and so small that about 635 of these cells could fit across the diameter of a penny.

Yet within the tiny confines of a cell, much has been packed, from organelles to a nucleus containing roughly six feet of coiled DNA if stretched out end-to-end. The space encased by the cell’s membrane is very busy and incompletely understood.

Researchers like Lorenzo Puri, MD, and Alessandra Sacco, PhD, at Sanford Burnham Prebys explore these tiny worlds, sorting out the signals and cues both inside and outside of cells that help dictate and determine normal development, health and aging.

About the art: Odra Noel is a medical doctor and PhD in basic science, with additional degrees in aesthetics and music. Her silk paintings focus primarily on human biology, often informed by microscopy. Wellcome Collection.

Mitochondria

Mitochondria are often called the “powerhouses of the cell.” They are responsible for most of the chemical energy that comes from breaking down carbohydrates and fatty acids. They produce 90% of the energy our bodies need to function, and also contain their own small chromosomes.

Given their fundamental importance, mitochondrial dysfunction is linked to diseases that affect almost every part of the body. Among them is the emperor of all maladies, cancer, in which tumors manipulate their mitochondria to boost survival and promote metastasis.

At Sanford Burnham Prebys, Kevin Tharp, PhD, is studying the interplay between mitochondrial metabolism and the physical properties of the tumor microenvironment, with a goal of identifying druggable mechanisms to undermine cancer’s malignant creativity. 

Meanwhile, Rolf Bodmer, PhD, Alexandre R. Colas, PhD, Georg Vogler, PhD, and others at Sanford Burnham Prebys are investigating the role of mitochondrial genes in hypoplastic left heart syndrome, a birth defect that accounts for 2-4% of congenital heart defects in the U.S., roughly 1,000 to 2,000 births per year. 

About the art: Odra Noel is a medical doctor and PhD in basic science, with additional degrees in aesthetics and music. Her silk paintings focus primarily on human biology, often informed by microscopy. Wellcome Collection.

Cell communications

Cells do not live in isolation. Their survival depends on how and how well they receive and process information from other cells and the surrounding environment. That communication or signaling can change their own internal workings in response. 

The inside of a eukaryotic cell is a very crowded and complex place. It begins with the nucleus, the cell’s control center and repository of genetic information. DNA replication, transcription and RNA processing all take place within the nucleus. 

Surrounding the nucleus are cellular organelles suspended in a gel-like fluid called cytoplasm. Each organelle has a definite structure and specific role: mitochondria produce energy for the cell; ribosomes make proteins; endoplasmic reticulum is a home for ribosomes; golgi apparatus prepare proteins and lipid molecules for use in other places inside and outside of the cell; lysosomes contain enzymes needed to break down cellular components for reuse or destruction. 

Cell biology has been the subject of study for centuries. Cells remain imperfectly understood, with new revelations occurring constantly. For example, Brooke Emerling, PhD, and colleagues have described a previously overlooked family of proteins called lipid kinases that are essential to maintaining the energy that cells need to grow and survive. 

Emerling and colleagues have also uncovered a new role for a neglected lipid in cell membranes that are connected to an ancient signaling system in cells that help human organs grow and control their size. 

About the art: Odra Noel is a medical doctor and PhD in basic science, with additional degrees in aesthetics and music. Her silk paintings focus primarily on human biology, often informed by microscopy. Wellcome Collection.

Apoptosis

Apoptosis is a form of programmed cell death that regulates the number of cells in the body to prevent any imbalance and to remove sick or old cells. When a new cell is produced, an old cell must be removed, usually by apoptosis. In cancer, however, cells divide and grow, and the process of apoptosis is impaired, resulting in large numbers of dysfunctional cancer cells which can result in a tumor.

At Sanford Burnham Prebys, researchers like Kristiina Vuori, MD, PhD, and Darren “Ben” Finlay, PhD, seek to use apoptosis as a therapeutic tool by reactivating it in cancer cells.

Cancer cells are often more vulnerable to cell death due to their dysregulated genetics. They become dependent on certain pathways while many normal cells have “back-up” system they can use to survive. Vuori, Finlay and colleagues search for drugs that can target these unique cancer cell vulnerabilities by testing many molecules and compounds, sometimes in combination, on patient cancer cells (personalized medicine) while also making sure the effects on healthy cells are minimized.

About the art: Odra Noel is a medical doctor and PhD in basic science, with additional degrees in aesthetics and music. Her silk paintings focus primarily on human biology, often informed by microscopy. Wellcome Collection.