Salk Institute Research Articles

Newspaper coverage of human-pig chimera research: A qualitative study on select media coverage of scientific breakthrough.

A recently published article in the journal Cell by scientists from the Salk Institute highlighted the successful integration of stem cells from humans in pig embryos. This marks the first step toward the goal of growing human organs in animals for transplantation. There has, to date, been no research performed on the presentation of this breakthrough in the media. We thus assessed early newspaper coverage of the chimera study, looking into the descriptions as well as the benefits and concerns raised by the study mentioned by newspaper sources. We looked at newspaper coverage of the human-pig chimera study in the two weeks after the publication of the article describing the breakthrough in Cell. This time period spanned from January 26 to February 9, 2017. We used the LexisNexis Academic database and identified articles using the search string "hybrid OR chimera AND pig OR human OR embryo." The relevant articles were analyzed using qualitative content analysis. Two researchers openly coded the articles independently using themes that emerged from the raw texts. Our search yielded 31 unique articles, after extensive screening for relevance and duplicates. Through our analysis, we were able to identify several themes in a majority of the texts. Almost every article gave descriptive information about the chimera experiment with details about the study findings. All of the articles mentioned the benefits of the study, citing both immediate- and long-term goals, which included creating transplantable human organs, disease and drug development, and personalized medicine, among others. Some of the articles highlighted some ethical, social, and health concerns that the study and its future implications pose. Many of the articles also offered reassurances over the concerns brought up by the experiment. Our results appeared to align with similar research performed on the media representation of sensitive scientific news coverage. We also explored the inconsistency between the tone of the titles and the articles that followed. However, it is still too early to speculate what impact the media will play in the public perception of this particular research.

Chemical mimics endurance training in mice

“Hitting the wall” is a familiar experience to people who push their bodies to the limit during a marathon or even in an unexpected bout of prolonged exertion. Biochemically speaking, this means the body’s tissues have used up their reserves of glucose. Exercise typically improves performance by teaching the body to oxidize fat for energy and to preserve glucose. But how that process works has remained unclear. A team of researchers led by Michael Downes and Ronald M. Evans of the Salk Institute for Biological Studies has now determined that one of the proteins in muscle that orchestrates this improved endurance is a transcription factor called PPARδ (Cell Metab. 2017, DOI: 10.1016/j.cmet.2017.04.006). The team also found that activating PPARδ with a compound called GW501516 enhanced endurance in mice without any training. Even “couch-potato” mice were able to run an additional 100 minutes before they hit the wall if they were

The brain within buildings

Any time he has an airport layover, neuroscientist Satchidananda Panda pulls out his cell phone, activates the light-meter app, and starts collecting data. To passersby, it probably looks like he’s trying to get a better mobile signal. But he’s really adding to the array of more than 100,000 data points he’s amassed on light levels in different buildings. Panda, who works at the Salk Institute in La Jolla, California, is collaborating with architect Frederick Marks, a visiting scholar at the laboratory, to characterize light in the built environment and how it affects people. Insights into how our brains process building contours and navigate spaces could some day help architects judge designs and fashion new ones. Image courtesy of Shutterstock/saiko3p. But the collaborations between neuroscientists and architects, and their aims, extend far beyond the impact of illumination. “How do you build a space that optimizes learning in young children?” asks Thomas Albright, a vision scientist at Salk. “How do you build a hospital that optimizes healing? How do you build a work environment that optimizes efficiency? The hope is that neuroscience can provide some of the answers.” The application of neuroscience to architecture remains in its infancy. No one has yet laid out all of the features necessary to design a building with direct roots in brain science, although architects certainly plan buildings with features meant to promote well-being. But Marks, a founding member and CFO of the Academy of Neuroscience for Architecture (ANFA), believes it will eventually be possible for neuroscience and cognitive science to inform design with greater rigor. In the last couple of years, scientists have begun to accumulate data on how our brains process buildings and navigate spaces, by monitoring brain activity or even using virtual reality environments (1⇓–3). Although data thus far are …

How HIV inserts DNA into hosts

When HIV infects a host cell, the pathogen converts its RNA code to DNA and then docks the genetic material in a host’s genome. The first glimpse of the HIV machinery that performs this insertion comes courtesy of a team of researchers led by Dmitry Lyumkis at the Salk Institute for Biological Studies (Science 2017, DOI: 10.1126/science.aah5163). Called the intasome, HIV’s insertion machinery is targeted and blocked by drugs such as raltegravir and elvitegravir. To develop these drugs and to study HIV’s intasome, scientists had relied on biochemical techniques, computer modeling, prior X-ray crystallography work describing individual domains within the insertion machinery and the structures of intasomes from related viruses, such as PFV, the prototype foamy virus. Lyumkis’s team used cryo-electron microscopy to image HIV’s intasome with a resolution of 3.5 to 4.5A. The group found that several amino acid residues in and near the machinery’s active site are positioned

Oxidized deoxyribonucleotides, mutagenesis, and cancer.

The FASEB JournalVolume 31, Issue 1 p. 11-13 PerspectiveFree to Read Oxidized deoxyribonucleotides, mutagenesis, and cancer Christopher K. Mathews, Corresponding Author Christopher K. Mathews [email protected] Department of Biochemistry and Biophysics, Oregon State University, Corvallis, Oregon, USACorrespondence: Salk Institute for Biological Studies, 10010 North Torrey Pines Rd., La Jolla, CA 92037, USA. E-mail: [email protected]Search for more papers by this author Christopher K. Mathews, Corresponding Author Christopher K. Mathews [email protected] Department of Biochemistry and Biophysics, Oregon State University, Corvallis, Oregon, USACorrespondence: Salk Institute for Biological Studies, 10010 North Torrey Pines Rd., La Jolla, CA 92037, USA. E-mail: [email protected]Search for more papers by this author First published: 11 October 2016 https://doi.org/10.1096/fj.201601100Citations: 1Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL No abstract is available for this article.Citing Literature Volume31, Issue1January 2017Pages 11-13 RelatedInformation

Enlisting the brain to treat diabetes

Some patients with diabetes inject themselves with insulin multiple times each day to keep their blood sugar at healthy levels. Researchers now report that a single injection of a protein called fibroblast growth factor 1 (FGF1) into the brains of diabetic rodents normalizes the animals’ blood glucose levels for at least 18 weeks (Nat. Med. 2016, DOI: 10.1038/nm.4101). The findings, the scientists say, suggest the brain plays a role in regulating how the liver and muscle handle glucose, and they point to the brain as a possible target for a diabetes therapy with sustained effects. Previous studies have shown that FGF1 plays a role in metabolism. Levels of FGF1 in the blood “go up when you eat and go down when you’re starving,” says Ronald Evans of the Salk Institute for Biological Studies, who was not involved in the new work. In 2014, Evans and colleagues showed that injecting FGF1

‏ארי בראל‎ [Ari Barell]. ‏מלך-מהנדס: דוד בן-גוריון, מדע ובינוי אומה‎ [Engineer-King: David Ben-Gurion, Science, and Nation Building]. ‏וט‎ + 338 pp., apps., bibl., index. ‏מכון בן-גוריון לחקר ישראל והציונות‎ [Sede Boqer: Ben-Gurion Research Institute for the Study of Israel and Zionism, 2014]. ₪55, $14.21 (paper).

Previous articleNext article No Access‏ארי בראל‎ [Ari Barell]. ‏מלך-מהנדס: דוד בן-גוריון, מדע ובינוי אומה‎ [Engineer-King: David Ben-Gurion, Science, and Nation Building]. ‏וט‎ + 338 pp., apps., bibl., index. ‏מכון בן-גוריון לחקר ישראל והציונות‎ [Sede Boqer: Ben-Gurion Research Institute for the Study of Israel and Zionism, 2014]. ₪55, $14.21 (paper).Tal GolanTal Golan Search for more articles by this author PDFPDF PLUSFull Text Add to favoritesDownload CitationTrack CitationsPermissionsReprints Share onFacebookTwitterLinkedInRedditEmail SectionsMoreDetailsFiguresReferencesCited by Isis Volume 107, Number 1March 2016 Publication of the History of Science Society Article DOIhttps://doi.org/10.1086/686208 Views: 146Total views on this site © 2016 by The History of Science Society. All rights reserved.PDF download Crossref reports no articles citing this article.

Inhibition of MARCH5 ubiquitin ligase abrogates MCL1-dependent resistance to BH3 mimetics via NOXA.

BH3 mimetic compounds induce tumor cell death through targeted inhibition of anti-apoptotic BCL2 proteins. Resistance to one such compound, ABT-737, is due to increased levels of anti-apoptotic MCL1. Using chemical and genetic approaches, we show that resistance to ABT-737 is abrogated by inhibition of the mitochondrial RING E3 ligase, MARCH5. Mechanistically, this is due to increased expression of pro-apoptotic BCL2 family member, NOXA, and is associated with MARCH5 regulation of MCL1 ubiquitylation and stability in a NOXA-dependent manner. MARCH5 expression contributed to an 8-gene signature that correlates with sensitivity to the preclinical BH3 mimetic, navitoclax. Furthermore, we observed a synthetic lethal interaction between MCL1 and MARCH5 in MCL1-dependent breast cancer cells. Our data uncover a novel level at which the BCL2 family is regulated; furthermore, they suggest targeting MARCH5-dependent signaling will be an effective strategy for treatment of BH3 mimetic-resistant tumors, even in the presence of high MCL1.

Safety and Clinical Benefit of Lentiviral Hematopoietic Stem Cell Gene Therapy for Wiskott-Aldrich Syndrome

Wiskott-Aldrich Syndrome (WAS) is an X-linked primary immunodeficiency characterized by thrombocytopenia, recurrent infections, eczema, autoimmunity and increased susceptibility to malignancies. Allogeneic hematopoietic stem cell transplantation (HSCT) is a recognized curative treatment for WAS, but is still associated with transplant-related complications and long-term morbidity, particularly in the absence of fully matched donors. In April 2010, we initiated a phase I/II clinical trial with hematopoietic stem cell (HSC) gene therapy (GT) for WAS. The investigational medicinal product (IMP) consists of autologous CD34+ HSC engineered with a lentiviral vector (LV) driving the expression of WAS cDNA from an endogenous 1.6 kb human WAS promoter (LV-WAS), infused after a reduced intensity conditioning (RIC) based on anti-CD20 mAb, targeted busulfan and fludarabine. We previously reported early follow up (FU) results from the first 3 patients (Aiuti et al., Science 2013). Seven patients (Zhu score ≥3) have now been treated at a median age of 1.9 years (1.1 - 11.1). As of May 2015, all patients are alive with a median FU of 3.2 years (0.7 - 5.0). CD34+ cell source was bone marrow (BM) (n=5), mobilized peripheral blood (MPB) (n=1) or both (n=1). IMP dose ranged between 7.0 and 14.1 x106 CD34+/kg, containing on average 94.4 ± 3.5% transduced clonogenic progenitors and a mean vector copy number (VCN)/genome in bulk CD34+ cells of 2.7 ± 0.8. No adverse reactions were observed after IMP infusion and RIC was well tolerated. Median duration of severe neutropenia was 19 days; granulocyte-colony stimulating factor was administered to 1 patient.In the first 6 treated patients with FU >2 years, we observed robust and persistent engraftment of gene corrected cells. At the most recent FU, transduced BM progenitors ranged between 20.7 and 59.7%, and LV-transduced cells were detected in multiple lineages, including PB granulocytes (VCN 0.34 - 0.93) and lymphocytes (VCN 1.18 - 2.73). WAS protein expression, measured by flow-cytometry, was detected in the majority of PB platelets [mean ± standard deviation (SD), 71.4 ± 14.0%], monocytes (63.3 ± 18.5%) and lymphocytes (78.9 ± 14.9%). Lymphocyte subset counts were normal in most patients and proliferative response to anti-CD3 mAb was in the normal range in all 6 patients.After immune reconstitution, a marked reduction in the annualized estimated rate of severe infections was observed, as compared with baseline (figure 1A). The first 6 treated patients discontinued anti-infective prophylaxis and no longer require a protected environment. Four patients stopped immunoglobulin supplementation and 2 of them developed specific antibodies after vaccination. Eczema resolved in 4 patients and remains mild in 2. No clinical manifestations of autoimmunity were observed ≥1 year after GT in accordance with improved B-cell development and decreased autoantibody production. All patients became platelet transfusion independent at a median of 4 months after GT (range: 1.0 - 8.7). Mean platelet counts progressively increased after treatment (mean ± SD: before GT, 13.4 ± 7.8 x109/l; 24-30 month FU, 45.8 ± 22.0 x109/l; 36-42 month FU, 57.0 ± 18.7 x109/l).The frequency and the severity of bleeding events decreased after the 1st year of FU. No severe bleedings were recorded after treatment (figure 1B).Quality of life improved in all patients after GT. From the 2nd year of FU, the number of hospitalizations for infections decreased and no hospitalizations due to bleeding were observed after treatment.The seventh patient treated, who received MPB derived CD34+ cells only, showed the fastest platelet recovery with the highest level of transduced myeloid cell engraftment, and is clinically well.No Serious Adverse Events (SAE) related to the IMP were observed. The most frequent SAE were related to infections (85%), occuring mainly during the 1st year of FU.Importantly, no evidence of abnormal clonal proliferations emerged after GT and the LV integration profile show a polyclonal pattern, with no skewing for proto-oncogenes.In conclusion, this updated report in 7 WAS patients show that GT is well tolerated and leads to a sustained clinical benefit. The high level of gene transfer obtained with LV-WAS results in robust engraftment of transduced HSC, even when combined with RIC. Prolonged FU will provide additional information on the long-term safety and clinical efficacy of this treatment. [Display omitted] DisclosuresVilla:Fondazione Telethon: Research Funding. Dott:GlaxoSmithKline: Consultancy. van Rossem:GlaxoSmithKline: Employment. Naldini:Salk Institute: Patents & Royalties: Lentiviral vectors; San Raffaele Telethon Institute: Patents & Royalties: Lentiviral vector technology; GlaxoSmithKline: Other: GSK licensed gene therapies developed at my Institute and the Institute receives milestone payments; Sangamo Biosciences: Research Funding; Biogen: Research Funding; Genenta Sciences: Equity Ownership, Membership on an entity's Board of Directors or advisory committees. Aiuti:GlaxoSmithKline (GSK): Other: PI of clinical trial which is financially sponsored by GSK; Fondazione Telethon: Research Funding.

Elizabeth Blackburn to lead Salk Institute

Elizabeth Blackburn to lead Salk Institute

Professor Michael Levitt

Professor Michael Levitt (Stanford University, USA) won the 2013 Nobel Prize in Chemistry for the development of multiscale models for complex chemical systems—computational tools which can calculate the course of chemical reactions. Professor Levitt was born in Pretoria, South Africa; he came to the UK on a summer vacation aged 16, where he decided to stay and study for his A‑levels. His interest in the physics of living systems drove him to study biophysics at King’s College London, before securing a PhD position at the Laboratory of Molecular Biology in Cambridge. In the interim year between his degree and beginning his PhD, Professor Levitt worked at the Weizmann Institute of Science in Israel, where he met his future wife. They married later that year and moved to Cambridge, where their three children were born. After completing his PhD, he spent time working in Israel, Cambridge, the Salk Institute and Stanford (both California). Since 1986, he has split his time between Israel and California. Outside of science, he is a keen hiker and he is well-known to have attended the eclectic ‘Burning Man’ Festival in California.[1]Professor Levitt visited the University of Warwick to speak at the Computational Molecular Science Annual Conference in March 2015. In this interview, Dr Gemma-Louise Davies, an Institute of Advanced Study Global Research Fellow, spoke to Professor Levitt about the importance of Interdisciplinarity in his field, role models in Academia, and his plans for the future.Image: Professor Michael Levitt (left) with Dr Scott Habershon (right, organiser of the 2015 Computational Molecular Science Annual Conference) during his visit to the University of Warwick in March 2015.[1] ‘Burning Man’ is a unique annual festival dedicated to community, art, music, self-expression and self-reliance. Tens of thousands of people flock to this temporary metropolis built in the Californian desert.

Learning how to learn with Prof. Barbara Oakley

Massive Online Open Courses or MOOCs are increasingly becoming visible with the advent of platforms like Coursera, which offer verified certificates. One of the more popular courses on Coursera is 'Learning How to Learn', which specifically targets students and provides them with a scientific basis for effective pedagogical techniques. The course is the brainchild of Prof. Barbara Oakley and her co-instructor, Terrence Sejnowski, the Francis Crick Professor at the Salk Institute. I recently had the opportunity to interview Prof. Barbara Oakley. This article is a summary of her responses.

Discovering the first tyrosine kinase

In the middle of the 20th century, animal tumor viruses were heralded as possible models for understanding human cancer. By the mid-1970s, the molecular basis by which tumor viruses transform cells into a malignant state was beginning to emerge as the first viral genomic sequences were reported and the proteins encoded by their transforming genes were identified and characterized. This was a time of great excitement and rapid progress. In 1978, prompted by the discovery from Ray Erikson’s group that the Rous sarcoma virus (RSV) v-Src–transforming protein had an associated protein kinase activity specific for threonine, my group at the Salk Institute set out to determine whether the polyomavirus middle T-transforming protein had a similar kinase activity. Here, I describe the experiments that led to the identification of a kinase activity associated with middle T antigen and our serendipitous discovery that this activity was specific for tyrosine in vitro, and how this in turn led to the fortuitous observation that the v-Src–associated kinase activity was also specific for tyrosine. Our finding that v-Src increased the level of phosphotyrosine in cellular proteins in RSV-transformed cells confirmed that v-Src is a tyrosine kinase and transforms cells by phosphorylating proteins on tyrosine. My colleague Bart Sefton and I reported these findings in the March issue of PNAS in 1980. Remarkably, all of the experiments in this paper were accomplished in less than one month.

Genesis of the Salk Institute: The Epic of Its Founders. By Suzanne Bourgeois. Berkeley (California): University of California Press. $49.95. xxxiv + 230 p.; ill.; index. ISBN: 978-0-520-27607-9. 2013.

Previous articleNext article No AccessReviews and Brief NoticesGenesis of the Salk Institute: The Epic of Its Founders. By Suzanne Bourgeois. Berkeley (California): University of California Press. $49.95. xxxiv + 230 p.; ill.; index. ISBN: 978-0-520-27607-9. 2013.Ilena GeorgeIlena GeorgeNeurology, School of Medicine, Yale University, New Haven, Connecticut Search for more articles by this author PDFPDF PLUSFull Text Add to favoritesDownload CitationTrack CitationsPermissionsReprints Share onFacebookTwitterLinkedInRedditEmail SectionsMoreDetailsFiguresReferencesCited by The Quarterly Review of Biology Volume 90, Number 2June 2015 Published in association with Stony Brook University Article DOIhttps://doi.org/10.1086/681445 Views: 9Total views on this site Copyright © 2015 by The University of Chicago Press. All rights reserved.PDF download Crossref reports no articles citing this article.

Genesis of the Salk Institute: The Epic of Its Founders by Suzanne Bourgeois (review)

Genesis of the Salk Institute: The Epic of Its Founders by Suzanne Bourgeois (review)

Divide and Conquer, Faster: Speeding Up Molecular Simulations

Divide and Conquer, Faster: Speeding Up Molecular Simulations

Kids and sports.

Kids and sports.

Human evolution. How we tamed ourselves--and became modern.

“Self-domestication” turned humans into the cooperative species we are today.

Editorial: advances in neuroscience: the BRAIN initiative and implications for neuroendocrinology.

Editorial: advances in neuroscience: the BRAIN initiative and implications for neuroendocrinology.

Stephen F. Heinemann: A true original.

Steve Heinemann, one of the founders of 21st century neuroscience, died on August 6, 2014. To those who had the honor to know him, “Stevie” was a man of personal and professional generosity, contagious energy, scientific integrity, and genuine enthusiasm. His death is a profound loss for all. Stephen F. Heinemann (1939–2014). Image courtesy of Joe Belcovson (The Salk Institute, La Jolla, CA). Steve Heinemann’s arc as a scientist traced that of modern neuroscience overall. Having earned a PhD from Harvard, followed by postdoctoral stints at the Massachusetts Institute of Technology and Stanford, Steve was one of a cadre of young bacteriophage geneticists who in the early 1970s decided to apply biochemistry and molecular biology to the study of nervous system development and function. Starting his own research group at The Salk Institute, where he spent the entirety of his career, Steve, like several of his contemporaries, adopted the neuromuscular junction as a tractable model synapse. This was a stand-in (or so it was believed at the time) for synapses in the brain. Whereas some studied the neuromuscular junction in frogs or … [↵][1]1To whom correspondence should be addressed. Email: lemke{at}salk.edu. [1]: #xref-corresp-1-1