- Michael H. Hecht Lab
- Synthetic Biology
- Alzheimer’s Disease
- Lab Group Photo
- Lab Photos
- Contact Information
Research in the Hecht group is focused in two areas:
(i) Synthetic Biology: From Protein Design to Artificial Genomes.
(ii) Alzheimer’s Disease: Molecular Underpinnings and the Search for Novel Therapeutics.
We have developed methods enabling the design and construction of vast combinatorial libraries of novel amino acid sequences. Most of these sequences fold into stable protein structures (see graphic at right), and many of them display biochemical activities. With the availability of millions of novel proteins, one can begin to go beyond “Protein Design” and consider of “Proteome Design.” This enables the exploration of new questions at the interface of chemistry and biology: Are natural proteins special? Or is it easy to produce new sequences that fold and function? (We think that latter is true). Since our collections of designed proteins are expressed from synthetic genes in living cells, we can now construct artificial “genomes” comprising sequences that never before existed in biology, but nonetheless can provide functions necessary to sustain the growth of living cells.
The image at right shows a ribbon diagram of the high-resolution 3-dimensional structure of S-824, a protein designed de novo in the Hecht laboratory
While our work in synthetic biology aims to design novel proteins that fold and function, our research on Alzheimer’s disease attempts to understand how this debilitating neurodegenerative condition is caused when natural proteins misfold and malfunction. A specific protein fragment known as A-beta has a propensity to misfold and aggregate into clumps. These aggregates are toxic and cause a range of cellular and neurological symptoms. Our research uses a combination of chemical and genetic approaches to (a) understand the molecular determinants of this aggregation, and (b) discover novel compounds that inhibit aggregation. Such compounds may ultimately serve as leads towards the discovery of novel therapeutics to treat Alzheimer’s disease.
The image at right is a collection of beta amyloid fibril pictures from "Mutations Enhance the Aggregation Propensity of the Alzheimer’s Aβ Peptide" by Woojin Kim and Michael Hecht.
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