Living and Breathing Science: Nature’s mystery revealed through testing countless hypotheses

A hypothesis is a tentative explanation for a phenomena or a prediction as to a possible outcome of an experiment. The hypothesis is the stock in trade of the scientist. Hypotheses can be simplistic or intricate and formulated from the tiniest bits of data. What any experienced scientist knows all too well is that most of her or his hypotheses will inevitably be proven wrong. But this does not stop us from generating hypotheses by the thousands in our efforts to solve nature’s mysteries. Indeed Mark Twain remarked that, “There is something fascinating about science. One gets such wholesome returns of conjecture out of such a trifling investment of fact.” His point is well taken, we must resist over interpreting our data and placing too much weight on our hypotheses. There may be few precious instances when findings from rigorous experimentation prove our hypotheses to be correct and a bit of nature's mystery is revealed.

Living and Breathing Science: A Milestone in Fibulin Research

In the 1980s, while working as a postdoctoral fellow with Erkki Ruoslahti in La Jolla, California, I discovered a protein that I later named fibulin from the Latin fibula for clasp. This year marked the twentieth year since my first publication on fibulin (which I pronounce FY-beau-lin). Over these two decades, many other investigators and I have built on the initial discovery. As a result, findings reported in nearly 400 manuscripts have revealed that fibulin (now called fibulin-1) is a member of family of eight extracellular matrix proteins having a variety of critical functions. One of the most significant roles to emerge for members of the fibulin family as a group is their ability to coordinate the assembly of elastic extracellular matrix fibers such as those that provide elasticity to blood vessels, lungs and skin.

Living and Breathing Science

As a boy growing up in Connecticut, when I wasn’t playing baseball, I was exploring the woods, ponds and streams in the forest behind my home, looking under rocks and logs and wading in the creeks and finding frogs, fish, tadpoles and insects. Little did I know that these were the formative experiences in my path to becoming a scientist. It has been a long journey to get where I am today as a scientist. As a result I have learned many lessons that I can impart to students and early stage researchers. In my blog series 'Living and breathing science' I will share my experiences in science and reveal my scientific credo.

NIH Funded Research is One Public Investment that Yields Enormous Returns

As a researcher who has been supported by grants from the National Institutes of Health (NIH) for over 20 years I am keenly aware of the largely prudent and accountable ways in which grant monies are spent by academic researchers. Dollar for dollar, the biomedical research enterprise may be one of the most cost effective of federally subsidized programs. I see first hand the enormous returns being paid on the taxpayer investment in biomedical research in the form of advancements in our understanding of disease mechanisms and new therapeutic approaches. In addition, federally funding of biomedical research directly and substantially benefits the American biotechnology industry. The days of biologists making their own reagents and gizmos to conduct experiments are long gone. Researchers now depend on a huge array of commercially available reagents, chemicals, consumables, kits and advanced instrumentation to conduct their investigations. Furthermore, a rising trend is to contract companies to provide highly specialized research services. In effect, this means that a large, and growing fraction of federal grant dollars are being funneled to U.S. companies that produce these goods and services. Therefore, an argument can be made that augmenting the NIH budget will stimulate the American biotechnology industry. I believe that this is indeed true and is only one of the reasons why I advocate doubling the NIH budget.

Shared Resource Facilities: Discovery Engines for Biomedical Research Institutions

In most academic biomedical research institutions, shared resource facilities exist to provide researchers access to state-of-the-art technologies. The services offered through these facilities are extremely valuable to advancing the research programs of investigators either by generating data for testing or developing scientific hypotheses. At the 2009 Southeast Institutional Development Award (IDeA) Regional Meeting held in Charleston, South Carolina on November 10th, I was a panelist in a session focusing on shared resource facilities. Based on my 13 years of experience as a director of shared resource facilities at the Medical University of South Carolina (http://proteogenomics.musc.edu/), I talked about issues related to sustaining financial support for shared resource facilities and incentivizing their use.

DiGeorge Syndrome Seminar at Medical College of Georgia

On October 23rd I presented a Grand Rounds seminar in the Department of Pediatrics at the Medical College of Georgia. In my lecture I conveyed evidence for the extracellular matrix protein fibulin-1 playing a critical role in the formation of the thymus, thyroid, cranial nerves, bones of the skull, blood vessels of the head, aortic arch arteries and outflow tract of the heart. The morphogenesis of all of these tissues involves contributions from a population of cells known as neural crest cells. Disorders of neural crest cells lead to congenital malformations referred to as neurocristopathies. The disorder, DiGeorge syndrome, is a human neurocristopathy having a range of clinical features including hypoparathyroidism, hypoplastic thymus or absent thymus, conotruncal heart defects (e.g., tetralogy of Fallot, interrupted aortic arch, ventricular septal defects, vascular rings) cleft lip and/or palate.
Our research shows that mice deficient in fibulin-1 display many of the abnormalities associated with DiGeorge syndrome. While 90% of individuals with DiGeorge syndrome have a deletion is a region of chromosome 22, specifically the q11.2 region, 10% of DiGeorge patients do not have this deletion. The fibulin-1 gene maps outside of the 22q11.2 region, located at 22q13.2. Ongoing research in my lab has implicated fibulin-1 a regulator of neural crest cell survival and migration during embryonic development. Furthermore, we have evidence that fibulin-1 regulates the expression of several genes previously implicated as being dysregulated in the pathogenesis of DiGeorge syndrome.