- Intern in Medicine, New Haven Hospital, Yale Medical School, 1942-1943
- Researcher, Department of Biological Chemistry, Harvard Medical School, 1941
- Student, College of the City of New York, 1933-1935
- M.D., Harvard Medical School, 1941
- A.B., Harvard College, 1937
The purpose of our research is to learn more about the physiological function and importance of the polyamines, and their role in health and disease.
The polyamines putrescine, spermidine, and spermine are major polybasic compounds in all living cells. Research indicates that these amines are important for many systems related to growth and differentiation. We are interested in their physiologic functions, mechanisms of polyamine synthesis, regulation of their biosynthesis and degradation, and how they act in vivo. For this purpose, we have constructed null mutants in each of the biosynthetic steps in both Escherichia coli and in Saccharomyces cerevisiae. These mutants cannot make these amines; hence they are very useful tools to study the physiological effects due to their deprivation.
Our research has focused on extending our studies on the biochemistry, regulation, and genetics of these amines and of the biosynthetic enzymes in S. cerevisiae and E. coli. Our work has demonstrated that the polyamines are required for growth of the organisms, their sporulation, maintenance of the killer dsRNA virus, protection against oxidative damage, protection against elevated temperatures, fidelity of protein biosynthesis, and for the maintenance of mitochondria. We have constructed clones that overproduce the various enzymes and have studied the sequence and structural characteristics of these enzymes. Our research has concentrated on the structure and regulation of ornithine decarboxylase, spermidine synthase, spermine synthase, and S-adenosylmethionine decarboxylase.
Most recently we have been studying the effect of polyamines in stimulating the level of the σ38 subunit (RpoS) of Escherichia coli RNA Polymerase, resulting in the induction of the glutamate decarboxylase-dependent acid response system.
Applying our Research
The polyamines are important in growth and development. We hope that this research will lead to effective therapies for various diseases such as cancer.
Need for Further Study
The physiologic function of these amines in bacteria, plants, and eukaryotes requires further study. This is particularly true for mammalian cells, including cancer cells. Eventually, we should consider studies on analogs with therapeutic importance.
- Escherichia coli glutathionylspermidine synthetase/amidase: phylogeny and effect on regulation of gene expression.
- Chattopadhyay MK, Chen W, Tabor H.
- FEMS Microbiol Lett (2013 Jan) 338:132-40. Abstract/Full Text
- Polyamines Stimulate the Level of the σ38 Subunit (RpoS) of Escherichia coli RNA Polymerase, Resulting in the Induction of the Glutamate Decarboxylase-dependent Acid Response System via the gadE Regulon.
- Chattopadhyay MK, Keembiyehetty CN, Chen W, Tabor H.
- J Biol Chem (2015 Jul 17) 290:17809-21. Abstract/Full Text
Research in Plain Language
We study compounds in the amine class. These include three polyamines—putrescine, spermidine, and spermine. Some amines are found in all living cells, and influence the growth and differentiation of organ systems. Our group studies how the body makes and breaks down these polyamines. We also study their physiologic functions and actions in living organisms. For this purpose, we developed bacteria and yeast with genetic mutations that prevent them from making these polyamines.
These genetically modified bacteria and yeast serve as very useful tools. We are using them to expand our knowledge in the studies of biochemistry, genetics, and enzymes. We are examining how organisms make these polyamines. We are also examining the physiological effects that occur when an organism lacks these polyamines.
Our group found that organisms require polyamines for many important functions. These include growth, reproduction, and protection. Polyamines are essential for accurate protein production. They also maintain cells’ “power plants” (mitochondria).