Overview

Recent Workshops:

AlphaFold at Vanderbilt: Molecular Basis of Genetic Diseases, Personalized Structural Biology and Center for Structural Biology are tying hands to host the seminar & workshop on alphafold on Tuesday, January 18, 2022, 9am-noon CST. Zoom @ https://vanderbilt.zoom.us/j/91707811398?pwd=QVA4MDErSEowZGlVQmsvODlIWnJ5QT09

Link to Vanderbilt Survey: https://redcap.vanderbilt.edu/surveys/?s=8KYXKL7FMF

About

The advent of rapid, economical genome sequencing has ushered in an unprecedented bold new age in medicine. Ever expanding DNA banks that link the genetic makeup of individuals with their electronic medical history are charting a transformational leap in patient care. The term “precision medicine” has been coined to refer to a new approach in disease treatment that synthesize and apply knowledge across the spectrum of biochemical research and clinical practice.

Mining the genetic databases has uncovered genetic dispositions to diseases as well associations of genes with particular phenotypes. However, these databases are also uncovering genetic diversity of unprecedented scales making direct correlation between nucleotide polymorphisms and disease predisposition difficult to ascertain. A more intricate understanding of the underlying molecular and cellular consequences of a particular variant are required to better predict its clinical expressivity.

Who we are

Vanderbilt University’s Program in the Molecular Basis of Genetic Diseases is a trans-institutional initiative to establish experimental and computational platforms to translate genetic discoveries into an understanding of the underlying molecular changes in protein structure, function and dynamics eventually culminating in the identification of therapeutic targets and strategies. It will leverage existing institutional investments in BioVU, methodological expertise for electronic health records data, techniques to determine the structure and dynamics of proteins and facilities for high throughput screening of small molecule targets. The vision of this program is to catalyze connections, collaborations, and cross-talk between clinicians, geneticists and basic scientists, thereby creating teams focused on understanding the relationships between genes and phenotypes. Unique to this effort, we will combine genetic association results with structural and computational biology and also with generation of animal models that are intrinsically amenable to mechanistic interrogation. These animal models will serve as a platform for phenotype characterization and subsequent high throughput screening.

What we can do

Overview

The Figure above is from a recent paper illustrating the molecular mechanism of mutation in the dopamine transporter associated with autism spectrum disorder in humans (collaboration between Galli, Mchaourab & Meiler labs, Proc Natl Acad Sci U S A. 2019 Feb 26;116(9):3853-3862). This study bridges structural biology, molecular neurosciences and organism physiology culminating in a mechanistic model that relates precise alteration in a transport cycle with behavioral manifestations in Drosophila. It is an example of how integration of approaches lead to new discoveries.

Investigators wishing to collaborate, especially including physicians at Vanderbilt University Medical Center are invited to contact our scientists with questions about specific Variants of Unknown Significance (VUS). We have the capacity to build 3D structural models of disease-associated proteins, generate testable hypotheses about the mechanism of disease, and test these hypotheses via protein cloning, expression, purification, and biophysical and biological functional assays. See more detail here.