A Cellular Passion

Adam Kuspa, Ph.D.
Background Dictyostelium imagery by M.J. Grimson & R.L. Blanton, Biological Sciences Electron Microscopy Laboratory, Texas Tech University

When Dr. Adam Kuspa began his career, he, like most young scientists, had set his sights on solving a scientific problem. In his case, the problem was cell differentiation—the way in which cells become specialized tissues in the body. It was and is one of the most critical biological and medical questions.

When he sought an organism in which he could study the problem in its simplest form, he decided upon Dictyostelium—or more properly Dictyostelium discoideum.

It is a simple organism with some complicating features. When food is plentiful, this simple soil amoeba exists as a single cell. However, if nourishment becomes hard to find or other stressors appear, these single cells give up their solitary existence to aggregate into a multicellular body consisting of two types of cells—pre-stalk and pre-spore. Eventually, it can become slug-like, capable of movement.

Today, Kuspa, the new chair of the Department of Biochemistry at Baylor College of Medicine, is known worldwide for his studies of differentiation and his leadership in the tightly knit world of Dictyostelium research. He led the team that sequenced the Dictyostelium genome. For his particular interest, Dictyostelium has proved an interesting and fruitful model organism.

For example, he said, the pre-stalk and pre-spore cells maintain a specific ratio.

"Take a multicellular slug and cut it in half, separating pre-stalk from pre-spore. Each half will reestablish the same proportion of the different kinds of cells on its own," he said.

The properties that permit this activity are a basic issue in the field of developmental biology and the understanding of cell differentiation, he said.

"It was at the time I got into the field 20 years ago, and it remains a burning question that people have gone on to study in flies, worms and mice," he said. "There is still room to learn in the area of how tissues interact, how the cell physiology in those tissues is altered and regulated and maintained in a specified differentiated state."

Colorized light micrograph by M.J. Grimson & R.L. Blanton

Yet differentiation is not the only area in which scientists find this unusual organism valuable. For example, Dictyostelium is representative of amoeba, which makes Dictyostelium important in the study of how such organisms can cause disease. Research by Kuspa and colleagues, for example, compared two amoeba genomes, identifying 40 genes unique to that group.

"We speculate that if any of those 40 genes are important in the growth of amoeba, they would make great drug targets in the treatment of diseases such as amoebic dysentery or hemolytic anemia (two diseases caused by amoeba)," he said.

Other properties of Dictyostelium make it an ideal method for studying how white blood cells seek out the infections they fight and how tumor cells spread throughout the body. More recently, researchers have discovered that it has a form of innate immunity that stems from ancestral origins.

The finding was exciting because proteins involved in Dictyostelium immunity were the same as some of those seen in humans, and Dictyostelium is the most primitive organism in which such proteins have been seen.

"We are looking for the proteins and the pathways in the cell that control this immunity and finding the same or similar proteins controlling (this kind of immunity) in mammals," said Kuspa.

A small organism has proved big answers to fundamental questions in biology, and Kuspa's participation in that was made possible by BCM's policy of allowing scientists to pursue their work and providing an environment in which such collaboration is encouraged. It is a philosophy he hopes to encourage as he directs the Department of Biochemistry in the future.

"A primary example of that was the (BCM) Genome Sequencing Center growing before my eyes just when we wanted to sequence the Dictyostelium genome," he said. "It happened so easily."

Not only does he hope to attract new scientists with a collaborative edge to the department, but the recent Ruth McLean Bowman Bowers Professorship gives him a chance to recruit an outstanding scientist to the department's faculty.

"It's a new challenge to create an environment where people want to participate in and collaborate on research," said Kuspa.

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Volume 3, Issue 1, Spring 2007


	A Cellular Passion by Ruth SoRelle, M.P.H. Adam Kuspa, Ph.D. Background Dictyostelium imagery by M.J. Grimson & R.L. Blanton, Biological Sciences Electron Microscopy Laboratory, Texas Tech University When Dr. Adam Kuspa began his career, he, like most young scientists, had set his sights on solving a scientific problem. In his case, the problem was cell differentiation—the way in which cells become specialized tissues in the body. It was and is one of the most critical biological and medical questions. When he sought an organism in which he could study the problem in its simplest form, he decided upon Dictyostelium—or more properly Dictyostelium discoideum. It is a simple organism with some complicating features. When food is plentiful, this simple soil amoeba exists as a single cell. However, if nourishment becomes hard to find or other stressors appear, these single cells give up their solitary existence to aggregate into a multicellular body consisting of two types of cells—pre-stalk and pre-spore. Eventually, it can become slug-like, capable of movement. Today, Kuspa, the new chair of the Department of Biochemistry at Baylor College of Medicine, is known worldwide for his studies of differentiation and his leadership in the tightly knit world of Dictyostelium research. He led the team that sequenced the Dictyostelium genome. For his particular interest, Dictyostelium has proved an interesting and fruitful model organism. For example, he said, the pre-stalk and pre-spore cells maintain a specific ratio. "Take a multicellular slug and cut it in half, separating pre-stalk from pre-spore. Each half will reestablish the same proportion of the different kinds of cells on its own," he said. The properties that permit this activity are a basic issue in the field of developmental biology and the understanding of cell differentiation, he said. "It was at the time I got into the field 20 years ago, and it remains a burning question that people have gone on to study in flies, worms and mice," he said. "There is still room to learn in the area of how tissues interact, how the cell physiology in those tissues is altered and regulated and maintained in a specified differentiated state." Colorized light micrograph by M.J. Grimson & R.L. Blanton Yet differentiation is not the only area in which scientists find this unusual organism valuable. For example, Dictyostelium is representative of amoeba, which makes Dictyostelium important in the study of how such organisms can cause disease. Research by Kuspa and colleagues, for example, compared two amoeba genomes, identifying 40 genes unique to that group. "We speculate that if any of those 40 genes are important in the growth of amoeba, they would make great drug targets in the treatment of diseases such as amoebic dysentery or hemolytic anemia (two diseases caused by amoeba)," he said. Other properties of Dictyostelium make it an ideal method for studying how white blood cells seek out the infections they fight and how tumor cells spread throughout the body. More recently, researchers have discovered that it has a form of innate immunity that stems from ancestral origins. The finding was exciting because proteins involved in Dictyostelium immunity were the same as some of those seen in humans, and Dictyostelium is the most primitive organism in which such proteins have been seen. "We are looking for the proteins and the pathways in the cell that control this immunity and finding the same or similar proteins controlling (this kind of immunity) in mammals," said Kuspa. A small organism has proved big answers to fundamental questions in biology, and Kuspa's participation in that was made possible by BCM's policy of allowing scientists to pursue their work and providing an environment in which such collaboration is encouraged. It is a philosophy he hopes to encourage as he directs the Department of Biochemistry in the future. "A primary example of that was the (BCM) Genome Sequencing Center growing before my eyes just when we wanted to sequence the Dictyostelium genome," he said. "It happened so easily." Not only does he hope to attract new scientists with a collaborative edge to the department, but the recent Ruth McLean Bowman Bowers Professorship gives him a chance to recruit an outstanding scientist to the department's faculty. "It's a new challenge to create an environment where people want to participate in and collaborate on research," said Kuspa.		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	Volume 3, Issue 1, Spring 2007



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