DNA2.0 Pro Bono Work
Synthetic Genes and Biobrick Synthesis for the University of Cambridge iGEM Team.
The enthusiastic and highly successful Cambridge iGEM team’s work engineering DNA devices for transcriptional tuning and pigment production in environmental biosensors won the 2009 iGEM Competition Grand Prize and First Prize in the Environment Track. “Cambridge won the Grand Prize at the iGEM Jamboree this morning – in no small part, no pun intended, due to your (DNA2.0’s) help” said Jim Haseloff, team advisor. DNA2.0 generously synthesized the entire expression optimized violacein operon, allowing the students to include five genes, each preceded by a ribosome binding site, flanked by their desired prefix and suffix, and held under a repressible promoter on the DNA2.0 pJexpress cloning vector.
Genes from DNA2.0 Aid Professor Eric Kremer in Developing Vectors to Treat Disease in Children and the Immunocompromised.
The clarification of virus-cell interactions is one of the most exciting aspects of modern virology. It may reveal similarities among virus families, the diversity of tropism, trafficking and pathogen propagation. The core study of my group at Institut de Génétique Moléculaire de Montpellier (IGMM) is the study of the adenovirus.
Adenovirus normally causes subclinical symptoms in humans, but in sporadic cases it can be lethal in infants and immunocompromised patients. In addition to fundamental virology questions, we have tried to modify a nonhuman adenovirus derived from canines to create a Trojan horse in order to deliver nucleic acids to cells in culture as well as in mammals. We have discovered that our canine adenovirus vectors preferentially infect neurons, have a high level of axonal transport and can express a transgenic element in the brain for greater than one year. With the help of DNA2.0, we are able to simplify the generation and production of vectors that could one day be used to treat neurodegenerative diseases such as mucopolysaccharidosis type VII—a global, orphan disease commonly affecting children—and Parkinson’s disease.
Professor Bengt Mannervik at Uppsala University Utilizes Synthetic Genes to Unlock the Power of Glutathione Transferases
Glutathione transferases (GSTs) are understood to play a prominent role in the cellular defense against mutagenic and carcinogenic chemical compounds. GSTs conjugate these noxious products with glutathione, inactivating electrophilic groups and facilitating their excretion. Because of this, GSTs are able to protect against various degenerative conditions including Alzheimer’s, Parkinson’s, cardiovascular diseases and cancer. GSTs also play an important role in hormone production and cellular signaling.
In humans, 17 discrete genes encoding the family of cytosolic GSTs have been recognized, each with its own separate spectra of detoxifying activity. However, only 16 of the corresponding proteins have been expressed and characterized, as the cognate mRNA of the 17th is unknown. Grad. Student Natalia Fedulova in Prof Mannerviks group is using a DNA2.0 synthesized gene with the predicted coding sequence of the last GST to express and functionally characterize this missing member of the GST family.
Prof. Chris Hill at University of Utah Use Synthetic Genes to Study the Ubiquitin-Proteasome System.
Numerous biological processes require the attachment of ubiquitin to proteins, including the widespread ubiquitin-proteasome system (UPS), which leads to the degradation of aberrant and regulatory proteins. A vast array enzymes act to conjugate polyubiquitin to proteins and dozens of other enzymes catalyze the removal of ubiquitin (deubiquitylation). These deubiquitylating enzymes (DUBs) facilitate complete substrate degradation, allow ubiquitin homeostasis, edit inappropriate or excessive ubiquitylation, and disassemble inhibitory unanchored ubiquitin chains.
In order to advance understanding of proteasome assembly and function, we are characterizing the structures of two key DUB proteins that appear to crop ubiquitin monomers from the distal end of polyubiquitin chains. Crystal structures of these proteins alone and in complex with each other and ubiquitin substrates will improve the understanding of ubiquitin-proteasome system and its role in protein degradation.