Portal de Periódicos da CAPES

Meet the Editors: David R. Goodlett

2018; Wiley; Volume: 32; Issue: 16 Linguagem: Inglês

10.1002/rcm.8187

1097-0231

David R. Goodlett,

Advanced Proteomics Techniques and Applications

We use mass spectrometry to study structure activity relationships (SARs) in biological molecules like lipids and proteins. In proteins this often comes in the form of clinical proteomic analysis most recently using longitudinal sampling to try to rescue biomarker discovery from pair-wise comparisons, but we also use chemical crosslinking to study protein–protein interactions. With lipids we are developing an SAR for lipid A, the component of lipopolysaccharide (LPS) that is responsible for initiating a cytokine cascade via Toll-like receptor 4. This lipid A SAR will help design better vaccine adjuvants and potentially anti-sepsis therapies. We are also developing a direct from source method for bacterial and fungal identification (Leung et al. Scientific Reports 2017). As a young boy I was active mowing lawns to make money. This meant I occasionally had to rebuild lawn mower engines with my Dad, which in turn meant keeping track of where all the small parts went in order to reassemble a functional engine. Equally important was the process of cleaning the parts and then tuning the engine when it was assembled. Working on mass spectrometers posed a similar challenge in getting a device in the right condition to carry out a task and where lots of small parts needing tracking and cleaning. From the chemistry side I was fascinated by molecular recognition between molecules and mass spectrometry presented an obvious way to study SARs. My first publication was entitled “Formylated peptides from cyanogen bromide digests identified by fast atom bombardment mass spectrometry” (Goodlett et al. Anal Biochem 1990). This work was done with my PhD advisor Richard B. van Breemen when we were at N.C. State University. We showed that the cyanogen bromide digestion of proteins created covalent modifications that tandem mass spectrometry could locate and assign. During my postdoctoral work with Richard D. Smith (1991–1993) we published one of the first studies using electrospray ionization mass spectrometry to determine a dissociation constant for a protein complex (Goodlett et al. J Am Soc Mass Spectrom. 1995; Loo et al. J Am Chem Soc. 1993). This field came to be known as Native MS. At the time electrospray was new making pretty much anything one did novel and exciting. Being passionate about what you do is fundamental to success no matter the occupation, but equally important is luck. Without the latter no matter how smart or clever one is, success is elusive. Luck on the other hand is mercurial. I started out college at Auburn University of Montgomery as a dual music and history major, but chemistry classes with Dr. John Teggins turned me on to the marvels of molecular interactions resulting in a change of major and transfer to Auburn University. Later while at Auburn, Dr. F.F. Skip Bartol in whose reproductive physiology laboratory I worked as a technician convinced me to study for my PhD. Like me he had struggled with the pull between science and music but eventually chose science. His life style of the laid back Professor raising money to answer interesting questions on your own time as your own boss, appealed to me. When they join the laboratory I tell them that I can't supply their passion. They have to have their own reasons to get out of bed everyday to be underpaid and overworked. From the beginning they all hear that they also need to be ready to be lucky. Many very smart people are never lucky, but if you are passionate about what you do then happiness is insured. They also hear me say that I don't care if they work 8 days a week or one because at the end they will be measured by their defense of testable hypotheses, not by their intent to be successful. The nontraditional uses of it like mass cytometry, which mimics flow cytometry, provides a clever outlet for immunologist or the ion knife, which is trying to bring mass spectrometry into the operating room, as well as breathe analysis for disease indication are all providing new opportunities for people who previously did not use mass spectrometry. Miniaturization of mass analyzers offers many new applications for the field, but miniaturization of the vacuum system is problematic. This has to be solved to provide true point of care devices, but this deficiency provides an opportunity for analytical chemists and physicists to develop new platforms. In the area of proteomics I feel that other technology will appear at some point, perhaps arrays or nanopore sequencing, that will supplant the role of mass spectrometry, which is a bit of a square peg in a round hole with regard to its use in proteomics. We make it work, but it is not efficient like genomics. Olympic weight lifting and playing guitar. Both present challenges that get my mind off my work. No matter how much you love your work, orthogonal breaks are refreshing for body and mind. Cooking, which I learned from my mother and grandmothers, is also a great distraction, but fundamentally it too is all about chemistry. Finally, I walk to work which takes about one hour round trip during which I enjoy interacting with homeless folk along the way and they just enjoy having someone to talk to about life. While I'm happy with my choice of science as a career, I would return to my roots and enroll in a jazz music school. Perhaps in France where I could also perfect my French language skills. In science we have teams made up of people from all over the world. Bringing these disparate people together helps bring down the conservative barriers that prevent progress and cooperation between cultures. Anthony Bourdain's swashbuckling approach to food and travel exploring the interfaces of food and government around the world provides new insights into how people live and work. His methods for embracing foreign food and cultures are inspiring. For more information on Dave and his research, please see goodlettlab.org and follow him on twitter at goodlettlab1.