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Scientists across the country are receiving Recovery Act funding through NIGMS. This support helps them accelerate the pace of important research and stimulate the economy by creating or retaining jobs and buying equipment. Here are some of their stories about how the funding has helped them.
Eric Alani, Cornell UniversityRoles for Mismatch Repair Proteins in Maintaining Genome Stability
Mismatch repair (MMR) systems have been identified in organisms ranging from baker's yeast to humans. They recognize and repair errors that occur when genetic material is duplicated. In humans, mutations in MMR genes have been correlated to a predisposition to hereditary forms of colorectal cancer (HNPCC). The goal of my laboratory is to understand at the mechanistic level how MMR proteins interact with each other to prevent errors that occur when genetic material is duplicated. We are addressing these questions in the model organism baker's yeast using a combination of genetic and biochemical approaches.
I proposed a new project for Recovery Act funding that is aimed at examining whether particular regions of an organism's genome are more susceptible to mutation than others. This work can allow us to understand why specific parts of a genome can undergo rearrangements that are associated with disease (e.g. cancers in humans). Like most places, Cornell University has experienced large budget cuts, layoffs, and hiring and pay freezes. Obtaining these funds has allowed me to retain one talented postdoctoral fellow and to hire a graduate student in the coming year. I am extremely grateful for this support and will make sure that it is spent wisely.
Michelle Arbeitman, University of Southern CaliforniaGenes Underlying Reproductive Behavior
My lab uses the fruit fly, Drosophila melanogaster, to understand how genes underlie complex behaviors. One behavior we have been studying is male courtship behavior, which in flies is a genetically specified behavior, allowing us to use powerful molecular-genetic tools to address behavioral questions. This will provide a basic understanding of how genes specify neural circuits and behavioral outputs. Despite the substantial gains in knowledge that scientists have contributed to in understanding many different realms of biology, we still have very limited understanding of the genetics of complex behaviors, which we hope to contribute toward.
I am very grateful to be a recipient of American Recovery Act funds from the National Institutes of Health. The additional resources allowed me to hire a postdoctoral fellow, maintain a technician in my laboratory at a full-time level and continue to employ undergraduates part-time during the school year. This has had a significant positive impact on many people's lives, including advancing scientific knowledge, maintaining diversity and fostering an excellent environment for the next generation of scientists that are being trained. Additionally, I was able to buy extra equipment that quickens the pace of all the work in my laboratory.
My institution, the University of Southern California, has benefited from Recovery Act funds, including from the NIH and NSF. Generally, this allows our research to be at the forefront and will allow a whole community of scientists to advance their research questions in important ways.
Thank you very much for supporting scientists!
Phil S. Baran, The Scripps Research InstituteTotal Synthesis of Anti-Cancer Natural Products
This grant funds a large portion of our lab that is interested in the total synthesis of anticancer natural products in efficient and innovative ways. These molecules have been chosen specifically because organic synthesis is the only means by which these valuable materials can be procured and evaluated for medicinal potential.
Our laboratory was on the verge of letting go three graduate students and two postdoctoral workers. We also would not be able to fund any summer outreach programs to employ high school students interested in science. Basically without this grant our laboratory would have been crippled. With this grant we have been able to retain our staff, hire new postdocs and continue our high school outreach program. We have been able to order supplies, chemicals and pay for spectroscopy and other necessary research services.
This is the best possible use of taxpayer money. The only way we can pay back our debts is to invest in science and innovation!
Susan Baserga, Yale UniversityAssembly, Localization and Function of the U3 snRNP
We're interested in how ribosomes—the factories in our cells that make proteins—are made. My lab has discovered 30 new proteins involved in this process. We're interested in the basic science of how cells grow and divide, in which ribosomes play a very important role. There are also connections to medicine. Other researchers have gone on to find rare genetic diseases associated with some of these proteins we've found.
I have had an NIH grant since I started as an assistant professor at Yale, but then my grant wasn't renewed and I had a gap in funding. I had to lay off my technician, who'd been with me for 5 years, and I was wondering what would happen with the three grad students and two postdocs who work in my lab. These are young people with very promising futures in science.
Getting Recovery Act funds is hugely helpful because it means that I can keep my laboratory together. I don't have to worry about my fellows and students now because we have funds for both their stipends and their supply money to carry out research. It's very important to us.
I've resubmitted my grant, and I'm crossing my fingers it will be funded. The Recovery Act money should stop the gap in the meantime.
Almira Correia, University of California, San FranciscoHepatic Degradation of Cytochrome P450 Enzymes
Cytochromes P450 are enzymes in the liver that break down drugs, toxins, cancer-causing agents and other chemicals. My project focuses on studying some of the proteins that break down the major P450s. These affect the way our bodies react to certain drugs, give rise to adverse drug-drug interactions and potentially lead to many diseases.
For me, the Recovery Act funding made the difference between being able to continue doing my research and having to retire. I had my retirement papers all lined up in case that became necessary. Without the Recovery Act funding, I would have had to basically fold up shop.
These funds have allowed me to continue to support my research and that of a key person involved in this project. I'm able to fund this fellow, who otherwise I would have had to let go, for another 2 years. He's been trained to do this work and he's at a critical point in the project. If I had let him go, I would have had to train somebody else from scratch, and these are not exactly easy experiments to conduct.
I've also hired a junior specialist/researcher part-time to do cell cultures. That's a new position, a new hire under this funding. And I have lined up a postdoc to join the lab starting in September. Her scientific background really fits well with the project.
I'm really grateful to the NIH for allowing me to continue almost 17 years of this research, and to enable it to come to some sort of fruition. The project is technically challenging, but we are finally at a stage where we are making significant progress in a very difficult area. Thus this funding came at a timely moment because our work is currently going quite well, and judging by the invitations to speak at four different international meetings, it is being recognized by my peers.
There are plenty of outstanding scientists who are in the same boat I am. I just consider myself extremely lucky that I'm able to continue, and I am sincerely grateful to the NIH for bailing me out.
Gray F. Crouse, Emory UniversityCellular Responses to Radiation and Other Types of Damage
We study S. cerevisiae, or baker's yeast, to learn more about DNA damage and repair. Sometimes DNA damage occurs through radiation exposure. Other times, it can be inherited. If the damage is not repaired, it can lead to mutation and genomic instability and cause health conditions such as cancer, aging and other diseases. Understanding how one of the most common forms of DNA damage—oxidative damage—causes mutations, and understanding the repair processes that prevent it, is extremely important in developing diagnostics and treatments.
I have had a lab at Emory for over 25 years, but after my initial start-up funds, there has not been a source of funds for purchasing equipment. The Recovery Act allowed us to acquire four new machines that are already improving the quantity and quality of our research. I knew that obtaining this new equipment would help our lab, but even so, I did not anticipate just how transformative it would be.
Our new colony counter has made the most significant enhancement to the lab. Before, it was not uncommon for someone to spend several hours counting yeast colonies from an experiment. That was tedious and easily led to errors. We also had no way of objectively dealing with colonies that were different sizes. With this new machine, we can reliably count plates with over 2,000 colonies in a few seconds – a fairly astounding result! We can also sort colonies into various size classes and count each class separately. This machine is already having major impacts on our research.
In addition to the colony counter, a new thermal cycler is saving us time and money by performing PCR reactions from microplate cultures of yeast.
Finally, two media preparation machines allow us to prepare 7 liters of media and pour plates automatically. We had been doing this by hand, which meant we could not prepare more than about 2 liters of media at a time. The machine is more cost-effective and also produces plates that are more uniform, reproducible and less prone to contamination and faulty preparation.
Tamara L. Doering, Washington University in St. LouisGlycan Biosynthesis in Cryptococcus neoformans
My research is in the broad area of microbiology, specifically studying fungi that cause disease. The microbe I study, Cryptococcus neoformans, is responsible for serious disease, mainly in people who are immunocompromised, like patients receiving cancer treatment, undergoing transplants or who have HIV. This disease has significant impact, with almost a million cases and 600,000 deaths worldwide in 2008. I study the basic biology of this deadly yeast, as well as how it interacts with human cells. This work is important for science understanding and for future development of therapies.
Through the Recovery Act, I received 2 years of NIGMS funding for a grant on studies of the surface capsule of Cryptococcus, a structure that is essential for its ability to cause disease. Despite a history of productivity in this area and positive feedback from peer reviewers, my grant application had missed the funding line. Now my research team is developing innovative methods and discovering new information about the microbe we study. This is advancing our understanding of basic biology and should have relevance to the future study of fungi, microbial pathogens and human disease.
This Recovery Act funding has allowed me to support a talented senior graduate student, a postdoctoral fellow and a technician. The fellow and the technician were new hires.
Beyond personnel, I have used the funding to obtain supplies, reagents and small equipment, most of it from local companies and almost all from sources within the United States. It has also been used for local services in Saint Louis City.
Finally, this funding allowed me to use the many hours it requires to revise and resubmit a proposal to focus on the science itself, a more cost-effective use of my professional time.
Larry Feig, Tufts Medical SchoolFunction of the Ras-Related Ral GTPase
Our research project attempts to define new anticancer targets by revealing the function of the Ral-GTPases, which are known to carry out some of the roles of Ras proteins in cancer.
The supplementary funds that we received from Recovery Act has allowed me to retain two key scientists involved in this project and replace faulty equipment that has slowed down our work in the past.
The NIH budget had not received any increase in funding in the past 8 years, which has amounted to a significant decrease when one takes into account inflation. This has truly hindered our cancer research that had been funded consistently from the NIH for the past 20 years. This Recovery money has helped make up some of that difference.
Julie Fiez, University of PittsburghBehavioral Brain Research Training Program
The overall goal of our training program is to enhance the training of graduate students who wish to study human behavior from a neural perspective. Thus, we aim to give this next generation of scientists the tools and experiences they need to understand how complex behaviors emerge from brain structure and function.
Our training program was reviewed very highly, but due to budget constraints within the NIH our funding was scaled back. This has meant that we are forced to turn away highly qualified students who are interested in our training program. Recovery Act funding has allowed us to support two new students through 2 years of training. These students are working in areas that are important for human health and so we are excited by how the investments of today will have a chance to impact the research findings of the future.
Susan Forsburg, University of Southern CaliforniaCheckpoints and Double Strand Breaks in S. Pombe Meiosis
We study meiosis—the division that turns cells with two sets of genes into gametes with one set—in S. pombe, a kind of yeast. Studying normal and abnormal events during meiosis in these cells can reveal insights into human health. More than half of human miscarriages result from defects during meiosis. This project examines how cells in meiosis respond to DNA damage to prevent defects from occurring.
I have hired a new technician with the Recovery Act-funded R01. His name is Morgan Hawkins, and he graduated from USC in 2008 (I taught him in Advanced Genetics). He wants to go to med school. Thanks to this grant, he'll be able to work with me for a year while he applies.
One of the things that makes Morgan's story different from other USC students is that he grew up nearby in south LA, which is a tough area. His family managed to send him and his siblings to private school, where he earned a scholarship and decided to go to Xavier University in New Orleans. But after his freshman year, Hurricane Katrina hit, and Morgan's academic records were destroyed along with most of the university itself. He returned to Los Angeles but shortly afterwards his father passed away.
Fortunately, USC has great outreach and gives local students generous scholarship opportunities. Morgan, who is African American, came to USC for his last 2 years and received a B.S. degree. Last year, he completed a UC Davis pre-med post-baccalaureate program for minority students. He hopes to begin medical school next fall.
I hired Morgan because he's smart and motivated, he asks terrific questions and he will be a great team addition. In just a few weeks, he's already making solid progress mastering the techniques he'll need to look at damage response proteins in meiosis. He'll get excellent laboratory experience under his belt before moving on to medical school, towards his ultimate goal of becoming a clinical researcher.
Robert D. Goldman, Northwestern UniversityIntermediate Filament Cell Surface Interactions
Intermediate filaments are structural proteins involved in cell shape, cell movement, early development and signal transduction. Many genetic mutations alter the structure or function of intermediate filaments to cause disease, including forms of muscular dystrophy, heart disease, cancer and many age-related disorders. Yet intermediate filaments' specific functions remain unknown. We conduct basic studies to understand their normal and defective functions.
Recovery Act funding saved several positions in our laboratory. It kept us from losing a technician, two graduate students and a postdoc. Now these slots are preserved for 2 years. This has helped us tremendously in keeping people on while we apply for grants.
Primarily, Recovery Act funding has kept several U.S. citizens in jobs, and secondarily, the rest of it is helping support the economy by letting us buy reagents and supplies.
The grant has extended our program in studying the structure and function of intermediate filaments. This is a general medical sciences grant, but because of its very basic nature, it is relevant to many different diseases. Part of the study the grant helped us finish is about a hot topic in cancer research known as the epithelial-mesenchymal transition.
This grant means a lot to us. This research has been going on for close to 30 years now, and a gap in funding would be devastating. We'd lose extremely talented people. We wouldn't be able to keep the lab going. It's been a great thing to be able to save jobs.
Caroline Kane, American Society for Cell BiologyThe Cell: An Image Library
In laboratories across the country, cell biologists collect terabytes of images and videos on a wide variety of cellular structures and processes, gene sequences, protein structures and more. But only a small fraction is ever shared. We are creating an
Image Library to house this rich data. It will provide a research tool allowing investigators to do virtual experiments with the data, asking and answering questions about normal and pathological processes that go beyond what the original researchers considered.
Recovery Act funding is essentially rescuing good data from oblivion. Incredibly, there has been no way for authors to share the vast bulk of their image data with the research community. Normally only a tiny fraction of the image data collected by researchers ever becomes public. Even the researchers themselves eventually lose access to their data, because they typically have no systematic way of archiving and preserving image data in searchable form. The Image Library creates a publicly accessible home for this "lost" data. It can also become a useful and searchable tool for educators and the curious general public.
Recovery Act funding has been absolutely essential to developing the infrastructure for the Library. That includes software development and hardware establishment as well as employing annotators and other professional personnel.
Even after the Recovery Act funding ends, this Library will continue to employ staff to expand the Library, conduct further research and develop new tools for searching and manipulating images and videos.
Joshua LaBaer, The Biodesign Institute at Arizona State UniversityDevelopment and Implementation of a Materials Repository for the PSI
Plasmids are circular pieces of DNA containing individual genes that are used for biological and biomedical experiments, including studying the structure and function of individual proteins, finding disease biomarkers and looking at drug responses. Once plasmids have been produced, researchers can share and use them as scientific tools.
Our laboratory hosts a repository of more than 250,000 plasmids that we have either made ourselves, received from Protein Structure Initiative (PSI) researchers as part of the NIGMS-funded structural genomics effort, or obtained from many sources willing to share. We distribute these plasmids to scientists in the United States and worldwide. Researchers can search for and request plasmids from the collection through the
DNASU website that also includes fully searchable annotations, associated publications and links to other biological databases for cross-referencing. We have distributed over 200,000 plasmids to researchers in more than 500 laboratories in 35 countries.
We received American Recovery and Reinvestment Act (ARRA) funding for a Nexus Universal BioStore -80 degree freezer storage and automated retrieval system. The freezer itself is 13,073 pounds fully loaded with samples. It is about 17.5 feet wide, 8.5 feet tall and 8 feet deep. It can store 855,000 tubes.
The Nexus system allows us to store glycerol stocks of our plasmid sample collection and easily retrieve and track these samples for distribution. Its primary benefit is its ability to "cherry pick" samples from within the collection. This saves time, safeguards our samples from cross-contamination and human error, and ensures that researchers will be able to receive materials from the repository more quickly—thus increasing the pace of scientific discovery.
Jon Lorsch, Johns Hopkins University School of MedicineKinetic Dissection of Eukaryotic Translation Initiation
We study protein synthesis, the final step in translating genes to proteins. Specifically, we look at the first stage, when a ribosome latches onto messenger RNA and finds the appropriate place to start "reading" it to make the corresponding protein. If the ribosome starts reading in the wrong place, it will make the wrong protein, which could be toxic to the cell.
We hope to learn why abnormal translation can lead to cancer and other diseases, and then figure out ways to reverse it. Also, the more we understand human protein translation and its differences from bacterial translation, the better we'll be able to make drugs that target bacterial cells and not human cells (i.e., antibiotics), or cancer cells and not normal cells.
Recovery Act funds will allow our lab to purchase a new protein purification system. Most of what we do requires large quantities of a lot of different purified proteins. This machine is the lifeblood of our lab. If we didn't have one, our research would grind to a sudden and complete halt.
I bought our current system when I first got to Johns Hopkins 10 years ago. It worked well over the long haul, but it's become obsolete. The company we bought it from no longer supports it and doesn't even make parts for it. We've been bandaging it together, literally with duct tape. Every time I looked at this thing, I was terrified—it was getting crankier and crankier, and things were starting to break more. If a screw broke, it would be the end. The day before I found out about the Recovery Act supplement, my tech told me that if he pressed the button to pause a purification run, the entire system shut down and the computer crashed. One minor glitch and days of work would be ruined.
This new system is going to be infinitely better. It will be faster, so it will increase our throughput. It will also allow us to do new experiments that weren't possible on the other system. It's a major benefit for the lab.
The equipment falls within a cost range that can be hard to fund otherwise.
We bought this product from a U.S. company, General Electric, which is going to help stimulate the economy and save jobs. But that's not the only benefit—the system is going to be used for research that hopefully will help find cures for diseases and may also spur innovations that will be used in the biotech industry. It's not just money going into the economy now, it's money being invested in research to drive the economy in the future.
Pierre Moenne-Loccoz, Oregon Health and Science UniversityNitric Oxide Reactions in Metalloenzymes
The goal of this research is to characterize mechanisms of nitric oxide (NO) detoxification employed by microorganisms to combat the mammalian immune response. In anoxic environments, the primary route of NO detoxification is reductive, with NO being converted to the inert gas N2O. In non-denitrifying microaerobic bacteria, archaea, and in some protozoan pathogens, this NO reduction reaction is catalyzed by iron-containing enzymes. The chemical steps behind the NO reduction at these metal centers remain to be define, and to do so, we combine rapid kinetic analyses with spectroscopic techniques.
The Recovery Act funding allowed for the replacement of a failing Krypton ion laser and accompanying chilling systems essential for the analysis of metalloproteins by resonance Raman spectroscopy. Since its installation in August 2010, the new ion laser has performed outstandingly as a source of excitation for the resonance enhancement of heme and nonheme iron centers. Because resonance Raman is a scattering technique, it is well suited for the analysis of freeze-quench trapped intermediates in the sub-millisecond to second timescales. The atomic level of information gained from vibrational spectroscopies such as Raman defines key parameters in enzyme-substrate interaction and chemical reactivity.
In the last 6 months, we have made significant breakthroughs in completing the characterization of diferrous-mononitrosyl complexes and showing that they are poised to react with a second NO. We can now generate these species to follow reactions with excess NO to trap the product of the next step in these catalytic reactions.
This research was carried out by two outstanding Ph.D. students who have now graduated, Takahiro Hayashi and Erik T. Yukl. They have experienced the awesome power of spectroscopy in seeing what none have seen before and they will undoubtedly be long-term contributors to the science community. During the lifetime of this laser, I hope to provide other graduate students the opportunity to develop their experimental skills and a passion for science.
Vincent Rotello, University of MassachusettsMagnetic Assembly, Supplement to Recognition and Presentation of Alpha Helices Using Nanoparticle Receptors
In this research we are using magnetic fields to guide cells and assemble them into controlled shapes for applications such as wound healing. In our process, we are using nanoparticles as "sheepdogs" that push the cells without actually binding to the cell surface. This lack of contact means that we should be able to remove the particles after we assemble the cells, minimizing issues of toxicity that can arise with current magnetic assembly strategies where magnetic particles are attached to or inside the cells.
We would not be able to pursue these studies without Recovery Act funding. The funds will be used to hire researchers in each of the three labs involved in the research, allowing us to nucleate a team and obtain proof-of-concept results for further funding.
Emily Scott and Jennifer Laurence, The University of KansasStructural Basis of Cytochrome P450 2A13 Activity
A recent Recovery Act supplement will allow us to explore a new approach to studying mammalian (membrane) cytochrome P450 enzymes. Since this family of enzymes is responsible for the clearance of drugs and for many adverse drug interactions, understanding them will allow us to better predict how drugs will work in the human body.
Currently we determine atomic structures of how various drugs and small molecules bind to cytochrome P450 proteins using X-ray crystallography, but this shows only static images of the protein alone or with its drug/small molecule, not how the protein accomplishes binding. Nuclear magnetic resonance (NMR) will allow us to observe these proteins in solution and to identify amino acids that interact with each substrate—and may ultimately tell us about the capabilities these proteins have to change shape to bind different drugs.
This project is extremely challenging and requires collaborating expertise from both the cytochrome P450 field, which Dr. Scott provides, as well NMR expertise, which is provided by Dr. Laurence. This supplemental grant from NIGMS supports our scientific collaboration and as well as addressing the goals of the Recovery Act by creating a new scientific position (postdoctoral fellow in the field of NMR) and supporting the purchase of equipment from American companies that will be used to generate the proteins we are studying.
Thanks to Recovery Act funds, we will be able to increase our understanding of how these enzymes work and potentially impact human health in a positive way. Through the parent grant and related grants, we are specifically studying the biochemistry of a cytochrome P450 from lung tissue and trying to design molecules that specifically inhibit only one of 57 different human cytochrome P450 enzymes. This particular cytochrome P450, 2A13, converts a nicotine derivative into two carcinogens that damage DNA in smokers. If the damage isn't repaired, it can ultimately result in lung cancer. Reducing lung DNA damage for the 22 percent of Americans who are smokers but cannot quit would both save lives and reduce health care costs.
Jenessa Shapiro, University of California, Los AngelesReducing Barriers to Gender Equity in STEM Fields
Although there has been progress over the past 30 years, women are still underrepresented in science, technology, engineering and math (STEM) fields. In contrast to many explanations that focus on biological or socialization factors, the concept of stereotype threat—defined broadly as a concern about confirming a negative stereotype about one's group—identifies how situational factors (e.g., proportion of women in one's workplace) lead to underperformance and underrepresentation of women in STEM fields. Our research project tests a set of interventions to reduce the pernicious effects of stereotype threat.
These Recovery Act funds are extremely helpful for keeping my lab running. Due to the budget crisis in California, one of my Ph.D. students was not going to receive funding. With this grant I will be able to fund her stipend and fund a new Ph.D.
We were also able to create a new job for a lab staff member. All three of these lab members are promising young scientists who are benefiting greatly by having this support.
We have also been able to order supplies and pay research participants—both integral to our research.
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