Susan Lindquist

Bio: Susan Lindquist is an academic researcher from Massachusetts Institute of Technology. The author has contributed to research in topics: Heat shock protein & Saccharomyces cerevisiae. The author has an hindex of 147, co-authored 440 publications receiving 81067 citations. Previous affiliations of Susan Lindquist include University of Illinois at Chicago & Howard Hughes Medical Institute.

Purification and properties of Hsp104 from yeast.

Abstract: Publisher Summary The chapter presents a study related to purification and properties of Hspl04 from yeast. The chapter describes protocols for the purification of wild-type heat shock protein 104 (Hspl04) from Saccharomyces cerevisiae and a rapid procedure for the purification of a modified version of Hspl04, carrying an amino-terminal histidine extension, from Escherichia coli . The chapter describes systems for the expression of toxic HSP100 proteins and mutant Hspl04 proteins. In addition, methods for determining the ATPase activity of the purified protein and its oligomerization properties are provided. The chapter mentions the biological and biochemical properties of Hsp104. Hspl04 is a heat-shock protein that promotes survival under extreme stresses, such as heat and high concentrations of ethanol. Hspl04 also functions in the maintenance and curing of a prion-like, protein conformation-based phenotype in yeast, referred to as [PSI + ], in which the translation termination factor Sup35 is sequestered into aggregates causing ribosomes to read through stop codons. To increase yield in S. cerevisiae , HSP104 can be expressed from high-copy vectors with strong promoters.

Detection of compounds that rescue Rab1-synuclein toxicity.

Abstract: Recent studies implicate a disruption in Rab‐mediated protein trafficking as a possible contributing factor to neurodegeneration in Parkinson's disease (PD). Misfolding of the neuronal protein α‐synuclein (asyn) is implicated in PD. Overexpression of asyn results in cell death in a wide variety of model systems, and in several organisms, including yeast, worms, flies, and rodent primary neurons, this toxicity is suppressed by the overproduction of Rab proteins. These and other findings suggest that asyn interferes with Rab function and provide new avenues for PD drug discovery. This chapter describes two assay formats that have been used successfully to identify small molecules that rescue asyn toxicity in yeast. The 96‐well format monitors rescue by optical density and is suitable for screening thousands of compounds. A second format measures viable cells by reduction of the dye alamarBlue, a readout that is compatible with 96‐, 384‐, and 1536‐well plates allowing the screening of large libraries (>100,000 compounds). A secondary assay to eliminate mechanistically undesirable hits is also described.

Withaferin a analogs and uses thereof

Abstract: The present invention provides a novel class of withanolides that have been isolated from W. somnifera under aeroponic conditions or produced semi-synthetically from withanolide natural products. The invention also provides pharmaceutical compositions thereof and methods for using the same in proliferative diseases, neurodegenerative diseases, autoimmune, and inflammatory diseases.

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

STRING v11: protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets.

Abstract: Proteins and their functional interactions form the backbone of the cellular machinery. Their connectivity network needs to be considered for the full understanding of biological phenomena, but the available information on protein-protein associations is incomplete and exhibits varying levels of annotation granularity and reliability. The STRING database aims to collect, score and integrate all publicly available sources of protein-protein interaction information, and to complement these with computational predictions. Its goal is to achieve a comprehensive and objective global network, including direct (physical) as well as indirect (functional) interactions. The latest version of STRING (11.0) more than doubles the number of organisms it covers, to 5090. The most important new feature is an option to upload entire, genome-wide datasets as input, allowing users to visualize subsets as interaction networks and to perform gene-set enrichment analysis on the entire input. For the enrichment analysis, STRING implements well-known classification systems such as Gene Ontology and KEGG, but also offers additional, new classification systems based on high-throughput text-mining as well as on a hierarchical clustering of the association network itself. The STRING resource is available online at https://string-db.org/.

Genome engineering using the CRISPR-Cas9 system

Abstract: Targeted nucleases are powerful tools for mediating genome alteration with high precision. The RNA-guided Cas9 nuclease from the microbial clustered regularly interspaced short palindromic repeats (CRISPR) adaptive immune system can be used to facilitate efficient genome engineering in eukaryotic cells by simply specifying a 20-nt targeting sequence within its guide RNA. Here we describe a set of tools for Cas9-mediated genome editing via nonhomologous end joining (NHEJ) or homology-directed repair (HDR) in mammalian cells, as well as generation of modified cell lines for downstream functional studies. To minimize off-target cleavage, we further describe a double-nicking strategy using the Cas9 nickase mutant with paired guide RNAs. This protocol provides experimentally derived guidelines for the selection of target sites, evaluation of cleavage efficiency and analysis of off-target activity. Beginning with target design, gene modifications can be achieved within as little as 1-2 weeks, and modified clonal cell lines can be derived within 2-3 weeks.

A program for annotating and predicting the effects of single nucleotide polymorphisms, SnpEff: SNPs in the genome of Drosophila melanogaster strain w1118; iso-2; iso-3

Abstract: We describe a new computer program, SnpEff, for rapidly categorizing the effects of variants in genome sequences. Once a genome is sequenced, SnpEff annotates variants based on their genomic locations and predicts coding effects. Annotated genomic locations include intronic, untranslated region, upstream, downstream, splice site, or intergenic regions. Coding effects such as synonymous or non-synonymous amino acid replacement, start codon gains or losses, stop codon gains or losses, or frame shifts can be predicted. Here the use of SnpEff is illustrated by annotating ~356,660 candidate SNPs in ~117 Mb unique sequences, representing a substitution rate of ~1/305 nucleotides, between the Drosophila melanogaster w1118; iso-2; iso-3 strain and the reference y1; cn1 bw1 sp1 strain. We show that ~15,842 SNPs are synonymous and ~4,467 SNPs are non-synonymous (N/S ~0.28). The remaining SNPs are in other categories, such as stop codon gains (38 SNPs), stop codon losses (8 SNPs), and start codon gains (297 SNPs) in...

Principles of Neural Science

Abstract: I have developed "tennis elbow" from lugging this book around the past four weeks, but it is worth the pain, the effort, and the aspirin. It is also worth the (relatively speaking) bargain price. Including appendixes, this book contains 894 pages of text. The entire panorama of the neural sciences is surveyed and examined, and it is comprehensive in its scope, from genomes to social behaviors. The editors explicitly state that the book is designed as "an introductory text for students of biology, behavior, and medicine," but it is hard to imagine any audience, interested in any fragment of neuroscience at any level of sophistication, that would not enjoy this book. The editors have done a masterful job of weaving together the biologic, the behavioral, and the clinical sciences into a single tapestry in which everyone from the molecular biologist to the practicing psychiatrist can find and appreciate his or