A. Baki Agbas

Nicole Ford, PhD
Assistant Professor of  Biosciences

Research Interest: Green production of silica-based biosensors, Predicting mutation  hotspots 

Diatom Genetic Engineering.Covered in silica shells (frustules), marine and/or brackish-water diatoms have great potential in a variety of fields such as biofuel production, delivery of cancer chemotherapeutics, and biosensors. Yet the very feature that makes them so attractive from a materials standpoint (i.e., their silica frustules), also makes them notoriously difficult to genetically modify. Recently, however, a new method for transforming diatoms was developed. Interspecies conjugation with bacteria is an affordable, rapid, and high-efficiency method of introducing DNA plasmids into diatoms that holds the potential to revolutionize the field of diatom biology. 

By transforming a plasmid containing a gene fusion between a silica-targeted protein and a functional protein of interest, the diatom frustule can be functionalized for a specific task (such as sensing, delivery, sequestration, remediation, etc.). Our current focus is to develop biosensors for various pathogenic agents (e.g., anthrax) using the diatom Thalassiosira pseudonana. Once the diatoms are engineered to express the biosensor protein in their frustules, the cultures could be scaled up to industrial levels - thereby creating an affordable green source of biosensors immobilized in silica. 

DNA-Intercalating Chemicals. Evolution and disease are both driven by DNA mutations. Certain small molecules can cause DNA damage by inserting themselves between and forming covalent adducts with neighboring DNA base pairs. Cells view these adducts as DNA damage, yet their repair is inherently error-prone. Therefore, repair of the damage from intercalating chemicals often results in DNA mutation. 

Specific rules for productive intercalation and adduct formation are not fully elucidated despite decades, if not centuries, of use and/or exposure to these chemicals. For example, medicinal uses of Psoralens have been reported for millennia, and 8-methoxypsoralen currently is used in conjunction with UVA light (PUVA treatment) for many dermatological ailments. 

Understanding whether specific gene sequences could be targeted and subsequently mutated due to psoralen photoadduct formation would help to predict the long-term side effects of these treatments. In addition to Psoralens, some other interesting examples of intercalating chemicals are: DNA alkylating agents used as cancer chemotherapeutics (e.g., mitomycin C and daunomycin) or the mutagenic agents from automobile exhaust (nitropyrenes) and cigarette smoke (benzo[a]pyrene diol epoxides).