The Goodson laboratory uses multifaceted approaches – biochemistry, molecular biology, bioinformatics – to address cell biological questions. We focus on the microtubule cytoskeleton – the dynamic network of protein fibers that pulls the chromosomes apart at mitosis, acts as "railroad tracks" for intracellular transport, and organizes the cytoplasm. How does this network form? What governs its dynamic turnover? How to other parts of the cell (organelles, chromosomes, the cell cortex) interact with microtubules? The answers to all of these questions lie in the biochemistry of tubulin and the proteins that interact with it.

Defining the behavior of the microtubule cytoskeleton on the basis of this biochemistry is the long-term goal of the Goodson laboratory. Because the microtubule cytoskeleton plays such a fundamental role in processes ranging from cell division to cell motility, these efforts have significance for medical issues ranging from cancer to neurodegenerative disease.

One focus at present is CLIP-170, a protein involved in both control of microtubule dynamics and in membrane-microtubule interactions. The plus (fast-growing) ends of microtubules play key roles in microtubule function because they control polymerization dynamics and also encounter potential cargo as microtubules explore space. CLIP-170 has the remarkable ability to dynamically track these growing microtubule plus ends, giving the appearance of "cellular fireworks". Why does CLIP-170 "surf" on microtubule ends? How does it track the growing ends? What is the functional significance of this behavior? We approach these questions through a combination of classic biochemistry (protein purification, in vitro assays), modern cell biology (time-resolved quantitative fluorescence microscopy), and biophysics.

Because it has recently become apparent that CLIP-170 is only one member of a large group of proteins that dynamically track microtubule plus ends, our efforts are expanding to encompass study of these additional proteins and the web of interactions between them. Notable examples include the colon-cancer associated protein APC, its binding protein EB1, and the dynein activator dynactin complex.

A second long-term interest in the Goodson laboratory is molecular evolution. While there is utility in establishing the history of protein families, our primary interest is in using this history to help understand what is happening now. As one example, biochemists have long used mutagenesis to dissect protein structure-function relationships. This is time and labor intensive. Instead, we use nature’s mutagenesis (the set of related sequences present in the genome databases) and combine it with bioinformatic techniques such as homology modeling to perform structure/function analysis.