Pamela Silver | |
---|---|
Born | Pamela Ann Silver |
Nationality | American |
Alma mater | |
Scientific career | |
Fields | Synthetic biology Systems biology [1] |
Institutions | |
Thesis | Mechanisms of membrane assembly : studies on the association of an integral protein with biological membranes (1982) |
Doctoral advisor | William T. Wickner |
Doctoral students | Christina Agapakis [2] Valerie Weiss |
Other notable students | Karmella Haynes Jessica Polka Anita Corbett |
Website | www |
Pamela Ann Silver is an American cell and systems biologist and a bioengineer. She holds the Elliot T. and Onie H. Adams Professorship of Biochemistry and Systems Biology at Harvard Medical School in the Department of Systems Biology. [1] [3] Silver is one of the founding Core Faculty Members of the Wyss Institute for Biologically Inspired Engineering at Harvard University. [4] [5]
She has made contributions to other disciplines including cell and nuclear biology, [6] [7] [8] systems biology, [9] [10] RNA biology, [11] [12] [13] cancer therapeutics, [14] international policy research, and graduate education. Silver was the first director of the Harvard University Graduate Program in Systems Biology. [15] She serves as a member of the National Science Advisory Board for Biosecurity. [16]
Silver grew up in Atherton, California, where she attended Laurel and Encinal Elementary Schools. During this time, she was a winner of the IBM Math Competition, winning a slide rule [17] and received special recognition for her early aptitude in science. She attended Menlo Atherton High School and graduated from Castilleja School in Palo Alto. She received her B.A. in chemistry from the University of California, Santa Cruz and her PhD in Biological Chemistry from the University of California, Los Angeles in 1982 in the laboratory of William T. Wickner, working largely on the coat assembly of the M13 coliphage. [18] [19]
Silver did her postdoctoral research with Mark Ptashne at Harvard University where she discovered one of the first nuclear localization sequences. [20] [21] She continued to study the mechanism of nuclear localization in her own lab as an assistant professor at Princeton University. During this time, she characterized the receptor for NLSs and discovered one of the first eukaryotic DnaJ chaperones. [22]
Silver continued in the area of Cell Biology upon moving to the Dana Farber Cancer Institute to hold the Claudia Adams Barr Investigatorship and to become Associate Professor of Biological Chemistry and Molecular Pharmacology at Harvard Medical School and Dana-Farber. During this time, she was among the first to follow GFP-tagged proteins in living cells. [23] In addition, she initiated early studies in systems biology to examine interactions within the nucleus on a whole genome scale. [24] Together with Bill Sellers, she discovered molecules that block nuclear export [25] and formed the basis for a publicly traded company Karyopharm Therapeutics. She was promoted in 1997 to Professor of Biological Chemistry and Molecular Pharmacology at Harvard Medical School and Dana-Farber.
In 2004, Silver moved to the newly formed Department of Systems Biology at Harvard Medical School as a Professor. Around this time, she worked closely with the Synthetic Biology Working Group at MIT and made the decision to move her research group into Synthetic Biology. She observed the motion of the carbon fixing organelles in photosynthetic bacteria. [26] She has worked extensively on designing modified bacteria to act as sensors for exposure to a drug [27] or inflammation [28] in the mammalian gut. She has served as the Director of an ARPA-E (DOE) project on electrofuels.
Her former students include Christina Agapakis, [2] Valerie Weiss, Karmella Haynes, Jessica Polka and Anita Corbett [29]
Some of Silver's work in this area includes the engineering of: mammalian cells to remember and report past exposures to drugs and radiation, [30] [31] [32] robust computational circuits in embryonic stem cells and bacteria, [33] and synthetic switches to moderate gene silencing with the integration of novel therapeutic proteins. [34] [35] Silver's work sets the stage for the development of novel therapies for use in both humans and animals.
Silver has characterized the carboxysome – the major carbon-fixing structure in cyanobacteria – to enhance photosynthetic efficiency [36] and carbon fixation. [37] She has also engineered cyanobacteria to more efficiently cycle carbon into high-value commodities and has shown that these bacteria can form sustainable consortia. [38] In a collaboration with Jessica Polka, Silver performed super-resolution microscopy of the β-carboxysome. [39]
Silver collaborated with Daniel Nocera at Harvard University to develop a device, called the "Bionic Leaf", that converts solar energy into fuel through a hybrid water-splitting catalyst system that leverages metabolically engineered bacteria. [40]
Silver discovered a correlation between nuclear transport and gene regulation – she identified the first arginine methyltransferase, which plays a role in chromatin function and is important to the movement of RNA binding proteins between the nucleus and cytoplasm of cells. She also discovered previously unknown variations among ribosomes that led her to propose a unique specificity for the matching between ribosomes and the subsequent translation of mRNAs. Silver's finding has several implications for our understanding of how gene regulation impacts disease development, such as cancer. [41]
Silver has been the recipient of an NSF Presidential Young Investigator Award, a Basil O’Connor Research Scholar of the March of Dimes, an Established Investigator of the American Heart Association, the NIH Directors Lecture, and NIH MERIT award, Innovation award at BIO, a Fellow of the Radcliffe Institute for Advanced Study, the Elliot T. and Onie H. Adams Professorship at Harvard Medical School and named the Top 20 Global Synthetic Biology Influencers. She sits on numerous advisory boards and has presented to members of the US Congress.
Silver was awarded the BBS Mentoring Award for Graduate Education at Harvard Medical School. She is also one of the founders of the International Genetically Engineered Machines competition (iGEM) and currently sits on the Board of iGEM.org. Silver founded and was the first Director of the Harvard University Graduate Program in Systems Biology. Silver was elected to the American Academy of Arts and Sciences in 2017 [42] and the National Academy of Sciences in 2023.
A spliceosome is a large ribonucleoprotein (RNP) complex found primarily within the nucleus of eukaryotic cells. The spliceosome is assembled from small nuclear RNAs (snRNA) and numerous proteins. Small nuclear RNA (snRNA) molecules bind to specific proteins to form a small nuclear ribonucleoprotein complex, which in turn combines with other snRNPs to form a large ribonucleoprotein complex called a spliceosome. The spliceosome removes introns from a transcribed pre-mRNA, a type of primary transcript. This process is generally referred to as splicing. An analogy is a film editor, who selectively cuts out irrelevant or incorrect material from the initial film and sends the cleaned-up version to the director for the final cut.
FtsZ is a protein encoded by the ftsZ gene that assembles into a ring at the future site of bacterial cell division. FtsZ is a prokaryotic homologue of the eukaryotic protein tubulin. The initials FtsZ mean "Filamenting temperature-sensitive mutant Z." The hypothesis was that cell division mutants of E. coli would grow as filaments due to the inability of the daughter cells to separate from one another. FtsZ is found in almost all bacteria, many archaea, all chloroplasts and some mitochondria, where it is essential for cell division. FtsZ assembles the cytoskeletal scaffold of the Z ring that, along with additional proteins, constricts to divide the cell in two.
Polyadenylation is the addition of a poly(A) tail to an RNA transcript, typically a messenger RNA (mRNA). The poly(A) tail consists of multiple adenosine monophosphates; in other words, it is a stretch of RNA that has only adenine bases. In eukaryotes, polyadenylation is part of the process that produces mature mRNA for translation. In many bacteria, the poly(A) tail promotes degradation of the mRNA. It, therefore, forms part of the larger process of gene expression.
The origin of replication is a particular sequence in a genome at which replication is initiated. Propagation of the genetic material between generations requires timely and accurate duplication of DNA by semiconservative replication prior to cell division to ensure each daughter cell receives the full complement of chromosomes. This can either involve the replication of DNA in living organisms such as prokaryotes and eukaryotes, or that of DNA or RNA in viruses, such as double-stranded RNA viruses. Synthesis of daughter strands starts at discrete sites, termed replication origins, and proceeds in a bidirectional manner until all genomic DNA is replicated. Despite the fundamental nature of these events, organisms have evolved surprisingly divergent strategies that control replication onset. Although the specific replication origin organization structure and recognition varies from species to species, some common characteristics are shared.
TEAD2, together with TEAD1, defines a novel family of transcription factors, the TEAD family, highly conserved through evolution. TEAD proteins were notably found in Drosophila (Scalloped), C. elegans, S. cerevisiae and A. nidulans. TEAD2 has been less studied than TEAD1 but a few studies revealed its role during development.
Histone deacetylase 3 is an enzyme encoded by the HDAC3 gene in both humans and mice.
Paired amphipathic helix protein Sin3a is a protein that in humans is encoded by the SIN3A gene.
Lymphoid enhancer-binding factor 1 (LEF1) is a protein that in humans is encoded by the LEF1 gene. It is a member of T cell factor/lymphoid enhancer factor (TCF/LEF) family.
Histone deacetylase 4, also known as HDAC4, is a protein that in humans is encoded by the HDAC4 gene.
Splicing factor U2AF 65 kDa subunit is a protein that in humans is encoded by the U2AF2 gene.
Histone deacetylase 5 is an enzyme that in humans is encoded by the HDAC5 gene.
Cell division cycle protein 27 homolog is a protein that in humans is encoded by the CDC27 gene.
YAP1, also known as YAP or YAP65, is a protein that acts as a transcription coregulator that promotes transcription of genes involved in cellular proliferation and suppressing apoptotic genes. YAP1 is a component in the hippo signaling pathway which regulates organ size, regeneration, and tumorigenesis. YAP1 was first identified by virtue of its ability to associate with the SH3 domain of Yes and Src protein tyrosine kinases. YAP1 is a potent oncogene, which is amplified in various human cancers.
Protection of telomeres protein 1 is a protein that in humans is encoded by the POT1 gene.
Protein Jumonji is a protein that in humans is encoded by the JARID2 gene. JARID2 is a member of the alpha-ketoglutarate-dependent hydroxylase superfamily.
Protein IWS1 homolog also known as interacts with Spt6 (IWS1) is a protein that in humans is encoded by the IWS1 gene.
Telomere-associated protein RIF1 is a protein that in humans is encoded by the RIF1 gene.
Polypyrimidine tract-binding protein 1 is a protein that in humans is encoded by the PTBP1 gene.
Ste5 is a MAPK scaffold protein involved in the mating of yeast. The active complex is formed by interactions with the MAPK Fus3, the MAPK kinase (MAPKK) Ste7, and the MAPKK kinase Ste11. After the induction of mating by an appropriate mating pheromone Ste5 and its associated proteins are recruited to the membrane.
WRAP53 is a gene implicated in cancer development. The name was coined in 2009 to describe the dual role of this gene, encoding both an antisense RNA that regulates the p53 tumor suppressor and a protein involved in DNA repair, telomere elongation and maintenance of nuclear organelles Cajal bodies.