Sea urchins and clams don’t fascinate most of us, yet Robert Goldman launched a remarkable research career in cell biology by gaining intimate knowledge about the cell’s nucleus and the process by which it disassembles during cell division, thanks, in part, to the eggs of clams and sea urchins. For decades his work year has been split between The Feinberg School of Medicine at Northwestern University in Chicago and at the Marine Biology Laboratory (MBL) in Woods Hole, Mass., where – of course -- there are clam and sea urchin eggs.
“It was very exciting, as my first exposure to the MBL from 1963-1965 coincided with the development of techniques for isolating mitotic spindles from sea urchin eggs. These preparations provided critically important insights into the biochemical and structural properties of the mitotic apparatus,” the complex machine that plays a crucial role in cell division and development.
What happens, or fails to happen, in the delicate dance of cell division is dependent on a complex series of structural changes in the interphase nucleus as it is dismantled, paving the way for the assembly of the mitotic spindle. These processes are deeply involved in organizing the chromosomes as a living cell reproduces itself. Such work has led Goldman into pioneering studies of obscure nuclear proteins called lamins, part of the scaffolding that keeps chromosomes in their places. His laboratory has made it clear that faulty lamins can lead directly to the disruption of normal nuclear functions such as DNA replication and gene transcription.
“We studied lamins for almost 25 years, over a period when very few laboratories were interested in these remarkable proteins,” Goldman recalled. “But now, and most dramatically, human diseases tell us that the lamins are certainly important. For example, in the gene for Lamin A there are hundreds of known mutations that cause a remarkable number of different diseases, including muscular dystrophies, heart disorders, and the early onset premature-aging ailment of children, commonly called progeria.”
Goldman’s fascination with the life sciences began when he was an undergraduate at the University of Vermont, because “I really got turned on to studying cell structure and function, especially in a protozoology course while looking at ciliates for the first time with a phase-contrast microscope.”
A native of Port Chester, N.Y., Goldman went from Vermont to Princeton University in 1963, where he received his Ph.D. degree in cell biology in 1967. It was in those years spending the summers in Woods Hole that the work on sea urchin and clam eggs began.
Goldman also won the American Cancer Society’s Eleanor Roosevelt fellowship, which took him to the United Kingdom for two years. His first post was in the pathology department at famed Hammersmith Hospital in London, followed by a year in the MRC Institute of Virology, in Glasgow, Scotland, where he concentrated on studies of the cytoskeleton of animal cells in culture.
“That’s when I first got interested in the family of intermediate filament proteins which is now known to contain the lamins,” he recalled. The lamins are stringy proteins related to hair and skin keratin, but are found only in the nucleus, where they play a structural role similar to what the cytoskeleton does in the main body of the cell, the cytoplasm. And research has shown there can be many, many genetic mutations that introduce flaws into this filamentous structure, and the flaws can cause disease.
“This is taking us on an exciting tour of the role structural proteins play in determining nuclear architecture,” Goldman said. “It’s opening up a new research area with profound implications for understanding the molecular mechanisms underlying the organization and regulation of chromosomes in the nucleus.”
Which means, of course, that lamins are playing critical roles in maintaining everyone’s health and welfare.