Susan Gottesman

Last updated

Susan Gottesman
Susan Gottesman NIH.jpg
Born (1945-05-19) May 19, 1945 (age 77)
New York, New York
Alma mater
Known for
Scientific career
Fields
  • Genetics
  • Microbial biology
Institutions
Thesis  (1972)

Susan Gottesman is a microbiologist at the National Cancer Institute (NCI), which is part of the National Institutes of Health. [1] Gottesman has been the editor of the Annual Review of Microbiology since 2008. [2]

Contents

She is a pioneer in the area of biological regulation in which enzymes that destroy specific other proteins, called proteases, play a central role inside the cell. She discovered and elucidated the central features of a new family of proteases that require energy for their function in the form of ATP-hydrolysis. [3] [4] She has also played a major role in the discovery and characterization of bacterial small RNAs. [5]

Early life and education

Gottesman was born on May 19, 1945, in New York. Her father was trained as an accountant and ran a company that made rotisseries and other small appliances. Her mother was a high school teacher and later became a guidance counselor. [4]

In fifth or sixth grade, Gottesman was given a book titled Microbe Hunters. [6] This book inspired her scientific career as she became fascinated with the importance and puzzling nature of scientific research. [6]

She continued her curiosity in science by attending a summer program in high school. It was a research opportunity held at Waldemar in Long Island, New York. [7] Gottesman attributed this opportunity to the emphasis on science and technology during the Cold War. [7] This experience helped fuel her passion for science, as she was introduced to genetics, DNA, cancer, and bacteria. [7]

Gottesman received a B.A. in biochemical sciences in 1967 from Radcliffe College and a Ph.D. in microbiology from Harvard University in 1972. [1] [8] She did her postdoctoral training from 1971 to 1974 in NCI's Laboratory of Molecular Biology. [8] From 1974 to 1976, she was a research associate at the Massachusetts Institute of Technology before returning as a senior investigator to NCI's Laboratory of Molecular Biology. [1] She is co-chief of that Laboratory and head of its Biochemical Genetics Section. [9]

Scientific contributions

Gottesman was a graduate student at Harvard in the 1960s and worked with Jon Beckwith. [5] Their work involved studying the lac operon to further understand the E. coli arabinose operon. [5] From their research, they were able to show that a transducing bacteriophage could work for the arabinose operon. Previous studies had only shown success in the lac operon, but the lambda phage was successful for the arabinose operon in her testing. [5] Gottesman's later research at the National Institutes of Health used this lambda phage to understand how bacteriophages are able to insert themselves into a bacterial chromosome and then subsequently remove themselves. [5]

Susan Gottesman is known for her work with small RNAs and ATP-dependent proteases. [5] Her work in these subjects has been celebrated by scientists such as Princeton University professor Thomas Silhavy and former Princeton professor David Botstein. [5] Gottesman focused her research on E. coli cells and the process of gene regulation. [1] She began studying the mechanism for energy-dependent proteolysis, but stumbled upon small RNAs in the process. [1] Small RNA are short RNA sequences that have a wide variety of functions within cells. [10] They have been shown to be vital in cell processes such as growth, cell differentiation, and defense. The small RNAs have also been shown to be a factor in certain diseases such as cancer, diabetes, and liver disease. [10]

The ATP-dependent proteases are shown to maintain the level of regulatory proteins and to get rid of any misfolded or damaged proteins. [3] They bind to their specific substrates by sequence recognition or by chemical and conformation interactions. [3]

In Gottesman's studies, she showed that the ATP-dependent proteases are regulated by the delivery of their substrate molecules by anti-adaptor and adaptor protein. [11] This finding has been shown of specific importance in the study of bacterial general stress response. [11] Along with the ATP-dependent proteases, the small RNA molecules are an important part of this response. [11]

For example, one of these small RNAs in Gottesman's research was found to positively regulate the translation of RpoS, a stress sigma factor of E. coli. [1] The DsrA small RNA helps to translate the RpoS factor by binding to the RpoS leader sequence. [1]

Awards and honors

Selected publications

Related Research Articles

In genetics, an operon is a functioning unit of DNA containing a cluster of genes under the control of a single promoter. The genes are transcribed together into an mRNA strand and either translated together in the cytoplasm, or undergo splicing to create monocistronic mRNAs that are translated separately, i.e. several strands of mRNA that each encode a single gene product. The result of this is that the genes contained in the operon are either expressed together or not at all. Several genes must be co-transcribed to define an operon.

<span class="mw-page-title-main">RNA polymerase</span> Enzyme that synthesizes RNA from DNA

In molecular biology, RNA polymerase, or more specifically DNA-directed/dependent RNA polymerase (DdRP), is an enzyme that catalyzes the chemical reactions that synthesize RNA from a DNA template.

<span class="mw-page-title-main">Rho factor</span> Prokaryotic protein

A ρ factor is a bacterial protein involved in the termination of transcription. Rho factor binds to the transcription terminator pause site, an exposed region of single stranded RNA after the open reading frame at C-rich/G-poor sequences that lack obvious secondary structure.

A sigma factor is a protein needed for initiation of transcription in bacteria. It is a bacterial transcription initiation factor that enables specific binding of RNA polymerase (RNAP) to gene promoters. It is homologous to archaeal transcription factor B and to eukaryotic factor TFIIB. The specific sigma factor used to initiate transcription of a given gene will vary, depending on the gene and on the environmental signals needed to initiate transcription of that gene. Selection of promoters by RNA polymerase is dependent on the sigma factor that associates with it. They are also found in plant chloroplasts as a part of the bacteria-like plastid-encoded polymerase (PEP).

<span class="mw-page-title-main">Endopeptidase Clp</span>

Endopeptidase Clp (EC 3.4.21.92, endopeptidase Ti, caseinolytic protease, protease Ti, ATP-dependent Clp protease, ClpP, Clp protease). This enzyme catalyses the following chemical reaction

The gene rpoS encodes the sigma factor sigma-38, a 37.8 kD protein in Escherichia coli. Sigma factors are proteins that regulate transcription in bacteria. Sigma factors can be activated in response to different environmental conditions. rpoS is transcribed in late exponential phase, and RpoS is the primary regulator of stationary phase genes. RpoS is a central regulator of the general stress response and operates in both a retroactive and a proactive manner: it not only allows the cell to survive environmental challenges, but it also prepares the cell for subsequent stresses (cross-protection). The transcriptional regulator CsgD is central to biofilm formation, controlling the expression of the curli structural and export proteins, and the diguanylate cyclase, adrA, which indirectly activates cellulose production. The rpoS gene most likely originated in the gammaproteobacteria.

The L-arabinose operon, also called the ara or araBAD operon, is an operon required for the breakdown of the five-carbon sugar L-arabinose in Escherichia coli. The L-arabinose operon contains three structural genes: araB, araA, araD, which encode for three metabolic enzymes that are required for the metabolism of L-arabinose. AraB (ribulokinase), AraA, AraD produced by these genes catalyse conversion of L-arabinose to an intermediate of the pentose phosphate pathway, D-xylulose-5-phosphate.

<span class="mw-page-title-main">HslVU</span>

The heat shock proteins HslV and HslU are expressed in many bacteria such as E. coli in response to cell stress. The hslV protein is a protease and the hslU protein is an ATPase; the two form a symmetric assembly of four stacked rings, consisting of an hslV dodecamer bound to an hslU hexamer, with a central pore in which the protease and ATPase active sites reside. The hslV protein degrades unneeded or damaged proteins only when in complex with the hslU protein in the ATP-bound state. HslV is thought to resemble the hypothetical ancestor of the proteasome, a large protein complex specialized for regulated degradation of unneeded proteins in eukaryotes, many archaea, and a few bacteria. HslV bears high similarity to core subunits of proteasomes.

<span class="mw-page-title-main">DicF RNA</span> Non-coding RNA

DicF RNA is a non-coding RNA that is an antisense inhibitor of cell division gene ftsZ. DicF is bound by the Hfq protein which enhances its interaction with its targets. Pathogenic E. coli strains possess multiple copies of sRNA DicF in their genomes, while non-pathogenic strains do not. DicF and Hfq are both necessary to reduce FtsZ protein levels, leading to cell filamentation under anaerobic conditions.

<span class="mw-page-title-main">DsrA RNA</span> Non-coding RNA

DsrA RNA is a non-coding RNA that regulates both transcription, by overcoming transcriptional silencing by the nucleoid-associated H-NS protein, and translation, by promoting efficient translation of the stress sigma factor, RpoS. These two activities of DsrA can be separated by mutation: the first of three stem-loops of the 85 nucleotide RNA is necessary for RpoS translation but not for anti-H-NS action, while the second stem-loop is essential for antisilencing and less critical for RpoS translation. The third stem-loop, which behaves as a transcription terminator, can be substituted by the trp transcription terminator without loss of either DsrA function. The sequence of the first stem-loop of DsrA is complementary with the upstream leader portion of RpoS messenger RNA, suggesting that pairing of DsrA with the RpoS message might be important for translational regulation. The structures of DsrA and DsrA/rpoS complex were studied by NMR. The study concluded that the sRNA contains a dynamic conformational equilibrium for its second stem–loop which might be an important mechanism for DsrA to regulate the translations of its multiple target mRNAs.

<span class="mw-page-title-main">RyhB</span> 90 nucleotide RNA

RyhB RNA is a 90 nucleotide RNA that down-regulates a set of iron-storage and iron-using proteins when iron is limiting; it is itself negatively regulated by the ferric uptake repressor protein, Fur.

<span class="mw-page-title-main">SgrS RNA</span>

SgrS is a 227 nucleotide small RNA that is activated by SgrR in Escherichia coli during glucose-phosphate stress. The nature of glucose-phosphate stress is not fully understood, but is correlated with intracellular accumulation of glucose-6-phosphate. SgrS helps cells recover from glucose-phosphate stress by base pairing with ptsG mRNA and causing its degradation in an RNase E dependent manner. Base pairing between SgrS and ptsG mRNA also requires Hfq, an RNA chaperone frequently required by small RNAs that affect their targets through base pairing. The inability of cells expressing sgrS to create new glucose transporters leads to less glucose uptake and reduced levels of glucose-6-phosphate. SgrS is an unusual small RNA in that it also encodes a 43 amino acid functional polypeptide, SgrT, which helps cells recover from glucose-phosphate stress by preventing glucose uptake. The activity of SgrT does not affect the levels of ptsG mRNA of PtsG protein. It has been proposed that SgrT exerts its effects through regulation of the glucose transporter, PtsG.

<span class="mw-page-title-main">ArcZ RNA</span>

In molecular biology the ArcZ RNA is a small non-coding RNA (ncRNA). It is the functional product of a gene which is not translated into protein. ArcZ is an Hfq binding RNA that functions as an antisense regulator of a number of protein coding genes.

<span class="mw-page-title-main">ATP-dependent Clp protease proteolytic subunit</span> Protein-coding gene in the species Homo sapiens

ATP-dependent Clp protease proteolytic subunit (ClpP) is an enzyme that in humans is encoded by the CLPP gene. This protein is an essential component to form the protein complex of Clp protease.

Bacterial small RNAs (bsRNA) are small RNAs produced by bacteria; they are 50- to 500-nucleotide non-coding RNA molecules, highly structured and containing several stem-loops. Numerous sRNAs have been identified using both computational analysis and laboratory-based techniques such as Northern blotting, microarrays and RNA-Seq in a number of bacterial species including Escherichia coli, the model pathogen Salmonella, the nitrogen-fixing alphaproteobacterium Sinorhizobium meliloti, marine cyanobacteria, Francisella tularensis, Streptococcus pyogenes, the pathogen Staphylococcus aureus, and the plant pathogen Xanthomonas oryzae pathovar oryzae. Bacterial sRNAs affect how genes are expressed within bacterial cells via interaction with mRNA or protein, and thus can affect a variety of bacterial functions like metabolism, virulence, environmental stress response, and structure.

<span class="mw-page-title-main">Bacterial DNA binding protein</span>

In molecular biology, bacterial DNA binding proteins are a family of small, usually basic proteins of about 90 residues that bind DNA and are known as histone-like proteins. Since bacterial binding proteins have a diversity of functions, it has been difficult to develop a common function for all of them. They are commonly referred to as histone-like and have many similar traits with the eukaryotic histone proteins. Eukaryotic histones package DNA to help it to fit in the nucleus, and they are known to be the most conserved proteins in nature. Examples include the HU protein in Escherichia coli, a dimer of closely related alpha and beta chains and in other bacteria can be a dimer of identical chains. HU-type proteins have been found in a variety of bacteria and archaea, and are also encoded in the chloroplast genome of some algae. The integration host factor (IHF), a dimer of closely related chains which is suggested to function in genetic recombination as well as in translational and transcriptional control is found in Enterobacteria and viral proteins including the African swine fever virus protein A104R.

The gene rpoN encodes the sigma factor sigma-54, a protein in Escherichia coli and other species of bacteria. RpoN antagonizes RpoS sigma factors.

Transcription-translation coupling is a mechanism of gene expression regulation in which synthesis of an mRNA (transcription) is affected by its concurrent decoding (translation). In prokaryotes, mRNAs are translated while they are transcribed. This allows communication between RNA polymerase, the multisubunit enzyme that catalyzes transcription, and the ribosome, which catalyzes translation. Coupling involves both direct physical interactions between RNA polymerase and the ribosome, as well as ribosome-induced changes to the structure and accessibility of the intervening mRNA that affect transcription.

A. C. Matin is an Indian-American microbiologist, immunologist, academician and researcher. He is a professor of microbiology and immunology at Stanford University School of Medicine.

Catherine Louise Kearney Squires was a microbiologist known for her work on ribosomal RNA using Escherichia coli as a model organism. She was an elected fellow of the American Academy of Microbiology and the American Association for the Advancement of Science.

References

  1. 1 2 3 4 5 6 7 "Susan Gottesman, Ph.D." Center for Cancer Research. August 12, 2014. Retrieved December 6, 2019.
  2. ↑ Ornston, Nick (2007). "Preface by Nick Ornston". Annual Review of Microbiology. 61. doi: 10.1146/annurev.mi.61.092607.100001 .
  3. 1 2 3 Koodathingal, Prakash; Jaffe, Neil E.; Kraut, Daniel A.; Prakash, Sumit; Fishbain, Susan; Herman, Christophe; Matouschek, Andreas (July 10, 2009). "ATP-dependent proteases differ substantially in their ability to unfold globular proteins". The Journal of Biological Chemistry. 284 (28): 18674–18684. doi: 10.1074/jbc.M900783200 . ISSN   0021-9258. PMC   2707231 . PMID   19383601.
  4. 1 2 Gottesman, Susan; Gant, Jason (October 1, 2008). "NCI Laboratory of Molecular Biology Oral History Project" (PDF).
  5. 1 2 3 4 5 6 7 "Prokaryotic Pioneer". The Scientist Magazine®. Retrieved December 6, 2019.
  6. 1 2 "Annual Reviews". www.annualreviews.org. Retrieved December 6, 2019.
  7. 1 2 3 Vanderpool, Carin K. (May 1, 2018). "Susan Gottesman: An Exceptional Scientist and Mentor". Women in Microbiology: 137–145. doi:10.1128/9781555819545.ch16. ISBN   9781555819538.
  8. 1 2 3 "Boston Bacterial Meeting". bostonbacterial.org. Retrieved December 6, 2019.
  9. ↑ Gottesman, Susan. "Susan Gottesman, Ph.D."
  10. 1 2 Zhang, Chunxiang (December 2009). "Novel functions for small RNA molecules". Current Opinion in Molecular Therapeutics. 11 (6): 641–651. ISSN   1464-8431. PMC   3593927 . PMID   20072941.
  11. 1 2 3 "Susan Gottesman, PhD | The Vallee Foundation". www.thevalleefoundation.org. Retrieved December 6, 2019.
  12. ↑ National Academy of Sciences. "Susan Gottesman". National Academy of Sciences. Retrieved March 15, 2015.
  13. ↑ American Academy of Arts & Sciences. "Dr. Susan Gottesman". American Academy of Arts & Sciences. Retrieved March 15, 2015.
  14. ↑ American Society for Microbiology (2009). "American Academy of Microbiology (AAM) 2009 Election Results". Microbe News (April). Archived from the original on April 2, 2015. Retrieved March 15, 2015.
  15. ↑ American Society for Microbiology (2011). "ASM News, 2011 General Meeting Awards". Microbe Magazine (April). Archived from the original on April 2, 2015. Retrieved March 15, 2015.
  16. ↑ National Academy of Sciences. "Selman A. Waksman Award in Microbiology". National Academy of Sciences. Archived from the original on March 18, 2015. Retrieved March 15, 2015.
  17. ↑ "Herbert Tabor Research Award". www.asbmb.org. Retrieved December 6, 2019.
  18. ↑ "6th Molecular Microbiology Meeting - Newcastle University". conferences.ncl.ac.uk. Retrieved December 6, 2019.
  19. ↑ "Four new VVPs appointed | The Vallee Foundation". www.thevalleefoundation.org. Retrieved December 6, 2019.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.