Small Science, Big Results
David Walt, director of the Walt Lab, with chemistry graduate students Ryan Hayman and Ragnhild Whitaker.
Most scientists can remember their first experiments. They usually occurred during childhood and were undertaken with the help of a junior chemistry set or whatever could be found around the house. Sometimes, these first forays into the world of science were a success. Other times, they were not.
For Ragnhild Whitaker, her first experiment was a little bit of both.
"I was going to trick my friend into drinking what she thought was hot chocolate," says Whitaker, a chemistry doctoral student. "It was hot chocolate, but there was also all sorts of gunk, spices, and nasty stuff in it. I made the drink, put it in a thermos, and then forgot about it. A few days later, my mom found it and the thermos was fuming. Eventually, the cap blew off."
While Whitaker's experiment was a failure on one level, since her subject failed to drink the concoction she had brewed, it was a success on another one--it showed her that small things can make a big impression.
Many years have passed since that first experiment, but Ragnhild Whitaker is still interested in the impact of small things. It's an interest she continues to explore as a member of the Walt Laboratory at Tufts University
"I'm currently performing research on how populations of cells behave on a single cell level," she says. "My main project concerns measuring receptor activation in thousands of single mammalian cells using a fiber-optic platform and a CCD camera."
By looking at thousands of single cells simultaneously, as opposed to groups, Whitaker hopes her work will help researchers produce better drugs, improve existing ones, and possibly provide new information about how the drugs activate the cells.
"The conventional method is to look at thousands of cells at once," says Whitaker. "Our method of single-cell analysis helps us get richer information and a lot more data. It enables us to see all the little things that can happen to each cell within these large groups. If you are able to see this, you will have a better idea of how drugs work on a single-cell level. It also enables researchers to detect outliers [cells which may cause harmful side effects] at an early stage."
New Ways of Measurement
Ragnhild Whitaker's work is part of the larger mission of the Walt Laboratory, which currently has eight Tufts Arts and Sciences graduate students conducting research in areas such as salivary diagnostics, vapor-based sensing (a research area being explored as a means of detecting the estimated 80 million landmines that are buried worldwide), cells, proteins, and DNA/RNA-based sensing.
"Our laboratory investigates new ways to measure things," says Professor David Walt, who is the director of the lab, the Robinson Professor of Chemistry at Tufts, and a Howard Hughes Medical Institute Professor. "We create very small arrays containing thousands of features that can easily fit on the head of a pin. Researchers in the laboratory use these arrays to study fundamental aspects of biochemistry, genetics, cell biology, olfaction, and they also develop practical ways to measure such things as water and air contamination."
The research of Ryan Hayman is a prime example of the lab's mission. Hayman, a chemistry doctoral student, is exploring how a person's saliva can help determine the type of asthmatic attack he or she is having. The work involves developing arrays of microsphere sensors to detect the different strains and species of pathogenic organisms present in a given saliva sample. These microarrays take advantage of the high feature density capable with 1 mm-diameter fiber optic bundles, each containing approximately 50,000 microsphere sensors. If the sensors that Ryan is developing can rapidly differentiate between viral or bacterial infection and give information on the species or strains present, then doctors will be able to quickly diagnose the cause of asthmatic exacerbations and treat patients accordingly.
This work is especially relevant today since, as the Environmental Protection Agency (EPA) reported in May 2006, asthma accounts for nearly 2 million emergency room visits each year and is the most common serious chronic disease of childhood.
"Our goal is to have a handheld device that will help doctors with the diagnosis process," says Hayman. "A lot of techniques for the diagnosis of chronic pulmonary inflammatory diseases are relatively crude. Current techniques involve taking a sample, culturing the sample, which takes a couple of days, and then determining which course of action to take. If the doctor knows an exacerbation is caused by a bacterial infection, the patient will get an antibiotic treatment. But that same antibiotic would be ineffective against a viral infection or exacerbation caused by an environmental allergen. Also, our sensors should be able to clue in doctors as to the level of antibiotic resistance, so drugs can be administered for maximum efficacy. Our hope is that doctors will be able to get meaningful results for the cause of exacerbation within a day, as opposed to a couple of days."
Hayman, who has also performed research on how to detect the algae that causes Red Tide, has seen some promising results thus far.
"We're about halfway through this phase of the saliva project and at this point I've done my initial proof of concept, where I took some saliva samples, amplified the DNA, and got a signal. I can detect some bacteria typically found lower in the airway. Right now, I'm working on designing a super-array for screening a whole range of things."
Hayman is not alone in this research. Fellow graduate students Timothy Blicharz and Chak Chow are also part of this work, as are a variety of outside institutions which, with Tufts, make up the Salivary Diagnostics Collaborative, an initiative supported by the National Institutes of Health's (NIH) National Institute of Dental and Craniofacial Research (NIDCR). These participating departments/institutions include the Tufts Computer Science Department, Boston University's Goldman School of Dental Medicine, the Data Coordinating Center at Boston University's School of Public Health, the Ahura Corporation, Boston Medical Center, Children's Hospital Boston, and the University of Pennsylvania.
"When I came to the Walt Lab, I realized that there were essentially two major things I could do," he says. "I could try to develop the chemistry, working with chemical reactions and doing the type of work that got us to the innovations of having beads in a fiber, or take stock of what kind of technology and techniques we have and look at applying them to a big problem. I think the latter was more interesting to me."
The Whole Graduate Student
The Walt Lab also strives to develop the whole graduate student who, by the time his or her graduate studies have concluded, is more than ready to succeed in their career of choice. To help bring this evolution about, Professor Walt treats each of his researchers as an individual.
"I've learned over the past twenty-five years that every student is different," says Walt, who estimates that over 50 graduate students have conducted research in his lab since he first came to Tufts during the early 1980s. "Everyone has their own needs, strengths, and weaknesses. What we try to do here at the lab is play to these strengths and develop skills for them to try to recognize and address their weaknesses."
One area Walt focuses on with many of his researchers is writing.
"All the papers that come out of the lab have a graduate student as the lead author, the first author on the paper," he says. "I think that training a Ph.D. or master's student to write is an important aspect of being a complete scientist. You need to be able to write cogently and present data in a readable fashion. Some people have had creative writing courses in college and often use very flowery words. You have to teach these students how to write a scientific paper. Other students do not have English as their first language and won't be used to writing a paper in English. I use the student's first draft of these papers as a way of helping them identify their weaknesses. Sometimes, this process takes more time than if I did the writing myself, but I wouldn't be doing my job as an educator if I didn't help students develop the skills they need to succeed."
While Walt works closely with his students on research papers, he gives them considerable autonomy and responsibility when it comes to their day-to-day research.
"I always tell my students that I'm their research advisor, not their research director," he says. "I don't tell them what to do. I advise them on their projects. The overall goals and the overall direction of the lab are developed by me as a I write grant applications and the funding that comes in is directed toward these larger goals, but everyone is responsible for their own project. For large projects, this approach means that students cannot leave their data processing to someone else. They have to be intimately involved with the nuts and bolts of the data they collect and how it gets processed. They learn skills such as how to deal with vendors and how to get instruments repaired. If they don't understand a procedure they have read about, I insist that they contact the author, even if the person is a famous scientist. I give them responsibility and once they have become accomplished at carrying out the research, planning experiments, designing the proper controls, running the experiments, collecting and analyzing the data, figuring out where to go next when the project succeeds, writing the paper, and going through all of the issues and problems with things breaking and things not working, they are then ready to get their Ph.D.s."
Adds Ragnhild Whitaker, "Professor Walt doesn't micromanage us. He encourages us to manage our own research. But he's definitely there if we hit a stop with our work."
The Walt Laboratory is supported by the National Institutes of Health's (NIH) National Institute of Dental and Craniofacial Research (NIDCR), National Institute of Allergy and Infectious Diseases (NIAID), National Institute of Biomedical Imaging and Bioengineering (NIBIB), as well as the Howard Hughes Medical Institute, U.S. Department of Defense, U.S. Department of Energy, National Science Foundation (NSF), and The Cooperative Institute for Coastal and Estuarine Environmental Technology (CICEET).
In 2006, Professor David Walt was named a Howard Hughes Medical Institute Professor. He can be reached at firstname.lastname@example.org
Article written by Robert Bochnak, G07
David Walt photo by Melody Ko
This article originally appeared in the winter 2007 edition of Alma Matters-Plus, an e-newsletter which highlights the work of Tufts graduate alumni, graduate students, and Tufts programs.