Brady’s first research focus is the development of new strategies for studying genetically encoded small molecules produced by bacteria that have not been grown in the lab. Soil microbes that have not yet been cultured outnumber their cultured counterparts by at least two to three orders of magnitude, making uncultured bacteria one of the largest pools of genetic diversity that remain unexamined for potentially useful natural products. Brady has worked extensively on the development of genetic strategies to access the vast chemical and biosynthetic potential of uncultured bacteria. His approach—which involves extracting this previously inaccessible DNA directly from environmental samples and cloning it in easily cultured bacteria—has allowed for the construction of large libraries of environmental DNA, as well as the development of methods to screen these libraries. His work has shown that these libraries are a promising source of both new derivatives of pharmacologically important classes of natural products, as well as completely novel families of bioactive natural products.