B for bureaucracy

Despite the scientific community''s overwhelming support for the European Research Council, many grant recipients are irked about red tapeThere is one thing that most European researchers agree on: B stands for Brussels and bureaucracy. Research funding from the European Commission (EC), which distributes EU money, is accompanied by strict accountability and auditing rules in order to ensure that European taxpayers'' money is not wasted. All disbursements are treated the same, whether subsidies to farmers or grants to university researchers. However, the creation of the European Research Council (ERC) in 2007 as a new EU funding agency for basic research created high hopes among scientists for a reduced bureaucratic burden.… many researchers who have received ERC funding have been angered with accounting rules inherited from the EC''s Framework Programmes…ERC has, indeed, been a breath of fresh air to European-level research funding as it distributes substantial grants based only on the excellence of the proposal and has been overwhelmingly supported by the scientific community. Nevertheless, many researchers who have received ERC funding have been angered with accounting rules inherited from the EC''s Framework Programmes, and which seem impossible to change. In particular, a requirement to fill out time sheets to demonstrate that scientists spend an appropriate amount of time working on the project for which they received their ERC grant has triggered protests over the paperwork (Jacobs, 2009).Luis Serrano, Coordinator of the Systems Biology Programme at the Centre for Genomic Regulation in Barcelona, Spain, and recipient of a €2 million ERC Advanced Investigator Grant for five years, said the requirement of keeping time sheets is at best a waste of time and worst an insult to the high-level researchers. “Time sheets do not make much sense, to be honest. If you want to cheat, you can always cheat,” he said. He said other grants he receives from the Spanish government and the Human Frontier Science Programme do not require time sheets.Complaints by academic researchers about the creeping bureaucratization of research are not confined to the old continent (see Opinion by Paul van Helden, page 648). As most research, as well as universities and research institutes, is now funded by public agencies using taxpayers'' money, governments and regulators feel to be under pressure to make sure that the funds are not wasted or misappropriated. Yet, the USA and the EU have taken different approaches to making sure that scientists use public money correctly. In the USA, misappropriation of public money is considered a criminal offence that can be penalized by a ban on receiving public funds, fines and even jail time; in fact, a few scientists in the USA have gone to prison.By contrast, the EU puts the onus on controlling how public money is spent upfront. Research funding under the EU''s Framework Programmes requires clearly spelt out deliverables and milestones, and requires researchers to adhere to strict accountability and auditing rules. Not surprisingly, this comes with an administrative burden that has raised the ire of many scientists who feel that their time is better spent doing research. Serrano said in a major research centre such as the CRG, the administration could minimize the paper burden. “My administration prepares them for me and I go one, two, three, four, five and I do all of them. You can even have a machine sign for you,” he commented. “But I can imagine researchers who don''t have the administrative help, this can take up a significant amount of time.” For ERC grants, which by definition are for ‘blue-skies'' research and thus do not have milestones or deliverables, such paperwork is clearly not needed.Complaints by academic researchers about the creeping bureaucratization of research are not confined to the old continentNot everyone is as critical as Serrano though. Vincent Savolainen at the Division of Biology at Imperial College London, UK, and recipient of a €2.5 million, five-year ERC Advanced Investigator Grant, said, “Everything from the European Commission always comes with time sheets, and ERC is part of the European Commission.” Still, he felt it was very confusing to track time spent on individual grants for Principal Investigators such as him. “It is a little bit ridiculous but I guess there are places where people may abuse the system. So I can also see the side of the European Commission,” he said. “It''s not too bad. I can live with doing time sheets every month,” he added. “Still, it would be better if they got rid of it.”Juleen Zierath, an integrative physiologist in the Department of Molecular Medicine at Karolinska Institutet (Stockholm, Sweden), who received a €2.5 million, five-year ERC grant, takes the time sheets in her stride. “If I worked in a company, I would have to fill out a time sheet,” she said. “I''m delighted to have the funding. It''s a real merit. It''s a real honour. It really helps my work. If I have to fill out a time sheet for the privilege of having that amount of funding for five years, it''s not a big issue.”Zierath, a native of Milwaukee (WI, USA) who came to Karolinska for graduate work in 1989, said the ERC''s requirements are certainly “bureaucracy light” compared with the accounting and reporting requirements for more traditional EU funding instruments, such as the ‘Integrated Projects''. “ERC allows you to focus more on the science,” she said. “I don''t take time sheets as a signal that the European Union doesn''t count on us to be doing our work on the project. They have to be able to account for where they''re spending the money somehow and I think it''s okay. I can understand where some people would be really upset about that.”…governments and regulators feel to be under pressure to make sure that the funds are not wasted or misappropriated…The complaints about time sheets and other bureaucratic red tape have caught the attention of high-level scientists and research managers throughout Europe. In March 2009, the EC appointed an outside panel, headed by Vaira Vike-Freiberga, former President of Latvia, to review the ERC''s structures and mechanisms. The panel reported in July last year that the objective of building a world-class institution is not properly served by “undue cumbersome regulations, checks and controls.” Although fraud and mismanagement should be prevented, excessively bureaucratic procedures detract from the mission, and might be counter-productive.Helga Nowotny, President of the ERC, said the agency has to operate within the rules of the EC''s Framework Programme 7, which includes the ERC. She explained that if researchers hold several grants, the EC wants recipients to account for their time. “The Commission and the Rules of Participation of course argue that many of these researchers have more than one grant or they may have other contracts. In order to be accountable, the researchers must tell us how much time they spend on the project. But instead of simply asking if they spent a percentage of time on it, the Commission auditors insist on time sheets. I realize that filling them out has a high symbolic value for a researcher. So, why not leave it to the administration of the host institution?”Particle physicist Ian Halliday, President of the European Science Foundation and a major supporter of the ERC, said that financial irregularities that affected the EU over many years prompted the Commission to tighten its monitoring of cash outlays. “There have been endless scandals over the agricultural subsidies. Wine leaks. Nonexistent olive trees. You name it,” he said. “The Commission''s financial system is designed to cope with that kind of pressure as opposed to trusting the University of Cambridge, for example, which has been there for 800 years or so and has a well-earned reputation by now. That kind of system is applied in every corner of the European Commission. And that is basically what is causing the trouble. But these rules are not appropriate for research.”…financial irregularities that affected the EU over many years prompted the Commission to tighten its monitoring of cash outlaysNowotny is sympathetic and sensitive to the researchers'' complaints, saying that requiring time sheets for researchers sends a message of distrust. “It feels like you''re not trusted. It has this sort of pedantic touch to it,” she said. “If you''ve been recognized for doing this kind of top research, researchers feel, ‘Why bother [with time sheets]?''” But the bureaucratic alternative would not work for the ERC either. This would mean spelling out ‘deliverables'' in advance, which is clearly not possible with frontier research.Moreover, as Halliday pointed out, there is inevitably an element of fiction with time sheets in a research environment. In his area of research, for example, he considers it reasonable to track the hours of a technician fabricating parts of a telescope. But he noted that there is a different dynamic for researchers: “Scientists end up doing their science sitting in their bath at midnight. And you mull over problems and so forth. How do you put that on a time sheet?” Halliday added that one of the original arguments in establishing the ERC was to put it at an arm''s length from the Commission and in particular from financial regulations. But to require scientists to specify what proportion of their neurons are dedicated to a particular project at any hour of the day or night is nonsensical. Nowotny agreed. “The time sheet says I''ve been working on this from 11 in the morning until 6 in the evening or until midnight or whatever. This is not the way frontier research works,” she said.Halliday, who served for seven years as chief executive of the Particle Physics and Astronomy Research Council (Swindon, UK), commented that all governments require accountability. In Great Britain, for instance, much more general accountability rules are applied to grantees, thereby offering a measure of trust. “We were given a lot of latitude. Don''t get me wrong that we allowed fraud, but the system was fit for the purpose of science. If a professor says he''s spending half his time on a certain bit of medical research, let''s say, the government will expect half his salary to show up in the grants he gets from the funding agencies. We believe that if the University of Cambridge says that this guy is spending half his time on this research, then that''s probably right and nobody would get excited if it was 55% or 45%. People would get excited if it was 5%. There are checks and balances at that kind of level, but it''s not at a level of time sheets. It will be checked whether the project has done roughly what it said.”Other funding agencies also take a less bureaucratic approach. Candace Hassall, head of Basic Careers at the Wellcome Trust (London, UK), which funds research to improve human and animal health, said Wellcome''s translation awards have milestones that researchers are expected to meet. But “time sheets are something that the Wellcome Trust hasn''t considered at all. I would be astonished if we would ever consider them. We like to work closely with our researchers, but we don''t require that level of reporting detail,” she said. “We think that such detailed, day-by-day monitoring is actually potentially counterproductive overall. It drives people to be afraid to take risks when risks should be taken.”…to require scientists to specify what proportion of their neurons are dedicated to a particular project at any hour of the day or night is nonsensicalOn the other side of the Atlantic, Jack Dixon, vice president and chief scientific officer at the Howard Hughes Medical Institution (Chevy Chase, MD, USA), who directs Hughes'' investigator programme, said he''d never heard of researchers being asked to keep time sheets: “Researchers filling out time sheets is just something that''s never crossed our minds at the Hughes. I find it sort of goofy if you want to know the truth.”In fact, a system based on trust still works better in the academic worldInstead, Hughes trusts researchers to spend the money according to their needs. “We trust them,” Dixon said. “What we ask each of our scientists to do is devote 75% of their time to research and then we give them 25% of their time which they can use to teach, serve on committees. They can do consulting. They can do a variety of things. Researchers are free to explore.”There is already growing support for eliminating the time sheets and other bureaucratic requirements that come with an ERC grant, and which are obviously just a hangover from the old system. Indeed, there have been complaints, such as reviewers of grant applications having to fax in copies of their passports or identity cards, before being allowed sight of the proposals, said Nowotny. The review panel called on the EC to adapt its rules “based on trust and not suspicion and mistrust” so that the ERC can attain the “full realization of the dream shared by so many Europeans in the academic and policy world as well as in political milieus.”In fact, a system based on trust still works better in the academic world. Hassall commented that lump-sum payments encourage the necessary trust and give researchers a sense of freedom, which is already the principle behind ERC funding. “We think that you have to trust the researcher. Their careers are on the line,” she said. Nowotny hopes ERC will be allowed to take a similar approach to that of the Wellcome Trust, with its grants treated more like “a kind of prize money” than as a contract for services.She sees an opportunity to relax the bureaucratic burden with a scheduled revision of the Rules of Participation but issues a word of caution given that, when it comes to EU money, other players are involved. “We don''t know whether we will succeed in this because it''s up to the finance ministers, not even the research ministers,” she explained. “It''s the finance ministers who decide the rules of participation. If finance ministers agree then the time sheets would be gone.”     

Improved assay-dependent searching of nucleic acid sequence databases

Nucleic acid-based biochemical assays are crucial to modern biology. Key applications, such as detection of bacterial, viral and fungal pathogens, require detailed knowledge of assay sensitivity and specificity to obtain reliable results. Improved methods to predict assay performance are needed for exploiting the exponentially growing amount of DNA sequence data and for reducing the experimental effort required to develop robust detection assays. Toward this goal, we present an algorithm for the calculation of sequence similarity based on DNA thermodynamics. In our approach, search queries consist of one to three oligonucleotide sequences representing either a hybridization probe, a pair of Padlock probes or a pair of PCR primers with an optional TaqMantrade mark probe (i.e. in silico or 'virtual' PCR). Matches are reported if the query and target satisfy both the thermodynamics of the assay (binding at a specified hybridization temperature and/or change in free energy) and the relevant biological constraints (assay sequences binding to the correct target duplex strands in the required orientations). The sensitivity and specificity of our method is evaluated by comparing predicted to known sequence tagged sites in the human genome. Free energy is shown to be a more sensitive and specific match criterion than hybridization temperature.     

Chemotaxis in Borrelia burgdorferi

Borrelia burgdorferi is a motile spirochete which has been identified as the causative microorganism in Lyme disease. The physiological functions which govern the motility of this organism have not been elucidated. In this study, we found that motility of B. burgdorferi required an environment similar to interstitial fluid (e.g., pH 7.6 and 0.15 M NaCl). Several methods were used to detect and measure chemotaxis of B. burgdorferi. A number of chemical compounds and mixtures were surveyed for the ability to induce positive and negative chemotaxis of B. burgdorferi. Rabbit serum was found to be an attractant for B. burgdorferi, while ethanol and butanol were found to be repellents. Unlike some free-living spirochetes (e.g., Spirochaeta aurantia), B. burgdorferi did not exhibit any observable chemotaxis to common sugars or amino acids. A method was developed to produce spirochete cells with a self-entangled end. These cells enabled us to study the rotation of a single flagellar bundle in response to chemoattractants or repellents. The study shows that the frequency and duration for pausing of flagella are important for chemotaxis of B. burgdorferi.     

Microbial Transport, Survival, and Succession in a Sequence of Buried Sediments

Abstract Two chronosequences of unsaturated, buried loess sediments, ranging in age from <10,000 years to >1 million years, were investigated to reconstruct patterns of microbial ecological succession that have occurred since sediment burial. The relative importance of microbial transport and survival to succession was inferred from sediment ages, porewater ages, patterns of abundance (measured by direct counts, counts of culturable cells, and total phospholipid fatty acids), activities (measured by radiotracer and enzyme assays), and community composition (measured by phospholipid fatty acid patterns and Biolog substrate usage). Core samples were collected at two sites 40 km apart in the Palouse region of eastern Washington State, near the towns of Washtucna and Winona. The Washtucna site was flooded multiple times during the Pleistocene by glacial outburst floods; the Winona site elevation is above flood stage. Sediments at the Washtucna site were collected from near surface to 14.9 m depth, where the sediment age was approximately 250 ka and the porewater age was 3700 years; sample intervals at the Winona site ranged from near surface to 38 m (sediment age: approximately 1 Ma; porewater age: 1200 years). Microbial abundance and activities declined with depth at both sites; however, even the deepest, oldest sediments showed evidence of viable microorganisms. Same-age sediments had equal quantities of microorganisms, but different community types. Differences in community makeup between the two sites can be attributed to differences in groundwater recharge and paleoflooding. Estimates of the microbial community age can be constrained by porewater and sediment ages. In the shallower sediments (<9 m at Washtucna, <12 m at Winona), the microbial communities are likely similar in age to the groundwater; thus, microbial succession has been influenced by recent transport of microorganisms from the surface. In the deeper sediments, the populations may be considerably older than the porewater ages, since microbial transport is severely restricted in unsaturated sediments. This is particularly true at the Winona site, which was never flooded.     

Preservation of Tetherin and CD4 Counter-Activities in Circulating Vpu Alleles despite Extensive Sequence Variation within HIV-1 Infected Individuals

The HIV-1 Vpu protein is expressed from a bi-cistronic message late in the viral life cycle. It functions during viral assembly to maximise infectious virus release by targeting CD4 for proteosomal degradation and counteracting the antiviral protein tetherin (BST2/CD317). Single genome analysis of vpu repertoires throughout infection in 14 individuals infected with HIV-1 clade B revealed extensive amino acid diversity of the Vpu protein. For the most part, this variation in Vpu increases over the course of infection and is associated with predicted epitopes of the individual''s MHC class I haplotype, suggesting CD8+ T cell pressure is the major driver of Vpu sequence diversity within the host. Despite this variability, the Vpu functions of targeting CD4 and counteracting both physical virus restriction and NF-κB activation by tetherin are rigorously maintained throughout HIV-1 infection. Only a minority of circulating alleles bear lesions in either of these activities at any given time, suggesting functional Vpu mutants are heavily selected against even at later stages of infection. Comparison of Vpu proteins defective for one or several functions reveals novel determinants of CD4 downregulation, counteraction of tetherin restriction, and inhibition of NF-κB signalling. These data affirm the importance of Vpu functions for in vivo persistence of HIV-1 within infected individuals, not simply for transmission, and highlight its potential as a target for antiviral therapy.