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Vazquez A.,Center for Systems Biology | Bertino J.R.,University of New Brunswick
Cancer Research | Year: 2013

Previous studies have documented the roles of transport via the reduced folate carrier, retention via polyglutamylation, and increased levels of the target enzyme, dihydrofolate reductase in sensitivity to methotrexate. Recent studies have shown that the mitochondrial enzymes in the cellular metabolism of serine, folate, and glycine are overexpressed in a subset of human cancers and that their expression is required for tumor maintenance. In this Perspective article, we propose that the expression of mitochondrial enzymes in the metabolism of serine and glycine, in addition to those involved in folate metabolism, are determinants of the response to methotrexate. Furthermore, we show that myc activation in tumors is associated with upregulation of these enzymes.Wepropose that patients whose tumors show this phenotype will be sensitive to folate antagonists targeting thymidylate or purine biosynthesis. © 2012 AACR. Source


Sazer S.,Baylor College of Medicine | Lynch M.,Indiana University Bloomington | Needleman D.,Center for Systems Biology
Current Biology | Year: 2014

The origin of the nucleus at the prokaryote-to-eukaryote transition represents one of the most important events in the evolution of cellular organization. The nuclear envelope encircles the chromosomes in interphase and is a selectively permeable barrier between the nucleoplasm and cytoplasm and an organizational scaffold for the nucleus. It remains intact in the 'closed' mitosis of some yeasts, but loses its integrity in the 'open' mitosis of mammals. Instances of both types of mitosis within two evolutionary clades indicate multiple evolutionary transitions between open and closed mitosis, although the underlying genetic changes that influenced these transitions remain unknown. A survey of the diversity of mitotic nuclei that fall between these extremes is the starting point from which to determine the physiologically relevant characteristics distinguishing open from closed mitosis and to understand how they evolved and why they are retained in present-day organisms. The field is now poised to begin addressing these issues by defining and documenting patterns of mitotic nuclear variation within and among species and mapping them onto a phylogenic tree. Deciphering the evolutionary history of open and closed mitosis will complement cell biological and genetic approaches aimed at deciphering the fundamental organizational principles of the nucleus. © 2014 Elsevier Ltd All rights reserved. Source


Kirby D.P.,Straus Center for Conservation | Buckley M.,University of Manchester | Promise E.,Harvard University | Trauger S.A.,Center for Systems Biology | Holdcraft T.R.,Harvard University
Analyst | Year: 2013

All stakeholders in cultural heritage share an interest in fabrication methods and material technology. Until now methods for analysis of organic materials, particularly proteins, have not been widely available to researchers at cultural institutions. This paper will describe an analytical method for the identification of collagen-based materials from soft tissue sources and show examples of its application to diverse museum objects. The method, peptide mass fingerprinting (PMF), uses enzymatic digestion of extracted proteins to produce a mixture of peptides. The mass spectrum of the mixture contains characteristic marker ions - a peptide mass fingerprint - which are compared to species-specific markers from references as the basis of identification. Preliminary results indicate that analysis of materials from aged samples, several different tissue types, and tanned or untanned materials yields comparable PMF results. Significantly, PMF is simple, rapid, sensitive and specific, has been implemented in a museum laboratory, and is being practiced successfully by non-specialists. This journal is © The Royal Society of Chemistry. Source


News Article
Site: http://www.nature.com/nature/current_issue/

Scientists hunting for academic jobs got a rare glimpse into the mysterious tenure-track hiring process. A blog post written by computational genomicist Sean Eddy at Harvard University in Cambridge, Massachusetts, outlined the steps that he and his colleagues have taken since November to evaluate nearly 200 applicants for a Harvard faculty position. Interviews for six candidates begin this week. A tweet by Eddy on 9 January attracted fresh attention to the blog post, with commenters applauding his efforts to lift the veil on the selection process. Holly Bik, a genomics and bioinformatics researcher at New York University who is applying for jobs, tweeted: Eddy is a co-chair of the hiring committee for the faculty position at Harvard’s FAS Center for Systems Biology, and only joined the faculty there in July 2015. He says that he wrote the blog post to clarify the hiring process, adding that he is not commenting on Harvard’s recruitment policy. “People don’t get a lot of information about what happens in one of these searches and what the selection criteria are,” he says. “I’m worried about people not applying because they think we’re not going to hire minorities or women or people who don’t have Harvard degrees.” Eddy described the first step as triage, in which three faculty members (including the two hiring committee chairs) review every application, spending about ten minutes on each one. He wrote that he is looking for a clear research question in the research proposal, and looks through the publication history and attached publications — not to scrutinize journal impact factors or citation counts, but to assess the quality, creativity and trajectory of a candidate’s scientific contributions. “I think a lot of the angsty gnashing of teeth about needing Nature/Science/Cell papers is self-inflicted by the candidates,” Eddy writes. Honours, grants and letters of recommendation count at this stage, too. Successful applications are then re-read by three faculty members randomly chosen from the entire eight-member committee. They take a more thorough look at the research aims and the publications. In the end, however, Eddy admits: “A lot of it comes down to intangibles, like whether people in the department get excited about a candidate’s research question,” he writes. Eddy noted that the applicant group was made up of only 21% female candidates and 5% from underrepresented minorities. Many — Eddy didn’t count the exact number — had done at least some of their training at Harvard. Bik responded to the blog post, noting that she avoided applying for Harvard positions because of the sheer volume of other jobs that she was also applying for. She decided to place her bets on positions where she thought she had the best chance of success. “I said: ‘I’m not going to apply for this one because I have other applications that I really need to focus more of my time on’,” she said in an interview. On Twitter, Eddy asked Bik’s advice on how to avoid applicants taking themselves out of the running so that employers can recruit from a broader pool of applicants: Bik also suggested in her blog comment that crowd-sourced job wikis — on which job applicants anonymously compile information about available faculty positions — would be good places for schools to encourage applications from people who might need a nudge. In his post, Eddy also wrote that he tries to consider his own implicit biases — such as those against women and minorities in science — during the shortlisting process. One way to measure these biases is with an online test designed by Harvard social ethicist Mahzarin Banaji and her colleagues. Eddy says that he has taken this test a few times — after starting at Harvard and again after reading the hiring committee’s guidelines. “I used to think that I don’t have such biases. … Now I know I have implicit biases,” he wrote in the blog post. To counteract them, he said he initially evaluated applications from women and minority candidates separately from those from men, and then combined the shortlists — but not to create quotas, he added. “It’s one of the few concrete things I can think of to do in a process like this, to force people including myself to have a conscious, slow, second look at their decisions,” Eddy said. “It’s a work in progress. These are tough issues.” Bioengineer Ian Holmes, an associate professor at the University of California, Berkeley, who has worked with Eddy in the past, commended him in a tweet: Holmes acknowledged his own bias in subsequent tweets, adding in an interview: “I find it regrettable that I am biased, but I think there is more shame in not acknowledging one’s bias than in having the bias.” Eddy’s post resonated with other faculty members who have been involved in recruitment. Joan Strassmann, an evolutionary biologist and professor at Washington University in St. Louis, tweeted: Strassmann has written for years about the challenges of hiring faculty members on her Sociobiology blog. “I don’t want anyone to not go into [academia] because it seems like a club with secret rules,” she said in an interview. In November, she wrote how the process is inherently unfair. “Our job is to hire an excellent scientist, colleague, and teacher,” she wrote. “There are likely to be others even better in the pool, but not discoverable by our imperfect techniques.” Bik says that increased transparency in hiring is good for applicants. Whereas some might have insider information about a position because of well-connected mentors, others may have to rely only on what they can find online. “I think that transparency and availability of information are extremely valuable to evening out the playing field.”


News Article
Site: http://www.biosciencetechnology.com/rss-feeds/all/rss.xml/all

University of Oregon scientists have found that strength in numbers doesn't hold true for microbes in the intestines. A minority population of the right type might hold the key to regulating good health. The discovery, based on research using zebrafish raised completely germ free, is reported in a paper published in the Nov. 11 issue of Cell Host & Microbe. The findings provide a path to study the function of each bacterial species in the gut and to eventually, perhaps, predict and prevent disease, says lead author Annah S. Rolig, a postdoctoral researcher in the UO's Institute of Molecular Biology. In the project, researchers watched for immune response as isolates of species of bacteria, normally associated with healthy zebrafish, were introduced one at a time and in combination into previously germ-free intestines of the fish. In a telling sequence, one bacterial species, Vibrio, drew numerous neutrophils, which indicated a rapid inflammatory response in one fish. Another species, Shewanella, inserted into a separate germ-free fish barely attracted an immune response. In a third germ-free fish, both species were introduced together and assembled with a ratio of 90- percent Vibrio to 10-percent Shewanella. The inflammatory response in the third fish was completely controlled by the low-abundance species. "Until now, we've only been able to capture proportional information, like you'd see displayed in a pie graph, of the makeup of various microbiota, in percentages of their abundance," Rolig said. "Biologists in this field have typically assumed an equal contribution based on that makeup." Low counts of a bacterial species generally have been discounted in importance, but slight shifts in the ratios of abundant microbe populations have been thought to have roles in obesity, diabetes and inflammatory bowel diseases such as Crohn's disease. That thinking is now changing, Rolig said. "The contribution of each bacterium is not equal. There is a per-capita effect that needs to be considered." The keystone - an important participant that functions to regulate a healthy microbiota - may reside in low-abundant bacterial species. The research team found through additional scrutiny that these species secreted molecules - for now unidentified - that allowed them to dampen the immune response to the whole community. "Now we've shown that these minor members can have a major impact. If we can identify these keystone species, and find that in a disease state one species may be missing, we might be able to go in with a specific probiotic to restore healthy functioning," said Rolig, who also is a scientist in the National Institutes of Health-funded Microbial Ecology and Theory of Animals Center for Systems Biology, known as the META Center, at the UO. To develop a model to capture per-capita contributions of microbes in a population, Rolig and her co-authors -- biology graduate student Adam R. Burns, microbiologist Brendan Bohannan of the Institute of Ecology and Evolution and biologist Karen Guillemin, director of the META Center -- turned to UO physicist Raghuveer Parthasarathy. His math-driven model, detailed in the paper, provides formulas that predict collective inflammatory responses of combinations of bacteria. "I'm really proud of this paper because it exemplifies an achievement of one of the major goals of the META Center for Systems Biology, namely to provide a predictive model of how host-microbe systems function," Guillemin said. "This experimental and modeling framework could be readily generalized to more complex systems such as humans, for example to predict disease severity in individuals with inflammatory bowel disease based on the pro-inflammatory capacity of their gut microbes as assayed in cell culture."

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