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 University
- Phil S. Baran, The Scripps Research Institute
- Susan Baserga, Yale University
- Almira Correia, University of California, San Francisco
- Larry Feig, Tufts Medical School
- Julie Fiez, University of Pittsburgh
- Susan Forsburg, University of Southern California
- Jon Lorsch, Johns Hopkins University School of Medicine
- Vincent Rotello, University of Massachusetts
- Emily Scott and Jennifer Laurence, The University of Kansas
Tell us your Recovery Act story at http://www.nigms.nih.gov/recovery/stories.htm.
Eric Alani, Cornell University
Roles 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 post-doctoral 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.
Phil S. Baran, The Scripps Research Institute
Total Synthesis of Anti-Cancer Natural Products
This grant funds a large portion of our lab that is interested in the total synthesis of anti-cancer 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 University
Assembly, 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 five 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 Francisco
Hepatic 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 two 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.
Larry Feig, Tufts Medical School
Function of the Ras-Related Ral GTPase
Our research project attempts to define new anti-cancer 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 eight 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 Pittsburgh
Behavioral 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 two 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 California
Checkpoints 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 two years and received a BS 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.
Jon Lorsch, Johns Hopkins University School of Medicine
Kinetic 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 ten 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.
Vincent Rotello, University of Massachusetts
Magnetic 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 Kansas
Structural 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% of Americans who are smokers but cannot quit would both save lives and reduce health care costs.
