Biochemistry and Molecular Biology Committee Faculty
The growth and division of eukaryotic cells is a highly regulated process. A variety of events important for successful division must be carried out in the proper order, at the proper time, and in the proper location. This coordinated series of events is described as the “cell division cycle” or “cell cycle”. Successful regulation of the cell cycle is paramount to the survival of single and multi-celled organisms ranging from budding yeast to man (Movie of dividing yeast courtesy of M. Tyers). Errors in this process usually result in cell death, and at times trigger the accumulation of oncogenic properties, leading eventually to cancer. In her lab, Dr. Miller studies regulatory proteins called cyclins that trigger coordinated cell division. Dr. Miller′s lab uses the model system Saccharomyces cerevisiae to carry out genetic, genomic, and biochemical assays on cyclin function.
The research of Dr. Hill deals with the genetic determinants of cell wall integrity in fungi. The cell wall is an essential component of fungal growth and morphogenesis, whose structure and metabolism are insufficiently understood. This laboratory is generating and characterizing mutant strains of the filamentous fungus Aspergillus nidulans, which have defects in cell wall structure. Among genes so far identified as being able to affect wall integrity in these mutants are two that code for novel (not previously characterized) proteins – the first is a probable Golgi apparatus transporter of nucleotide sugars and the second is a probable plasma membrane structural protein. The specific functions of these proteins are under investigation.
Research in the Jackson-Hayes lab focuses on investigating regulatory mechanisms of eukaryotic gene expression, focusing on genes that are involved in fungal cell wall metabolism. The fungal cell wall, which is composed of polysaccharides and glycoproteins, is essential for growth and metabolism of the fungus and is an excellent target for antifungal drugs. We have identified several genes that play specific roles in cell wall metabolism in the filamentous fungus Aspergillus nidulans including genes that have homologues that have been found to be involved in establishing and maintaining cell wall integrity in yeasts and several other previously uncharacterized genes. Experiments are being conducted to investigate the regulation of message production of these genes, to observe the cellular localization of the proteins during different stages of fungal development, and to learn more about the specific role of each of them in cell wall metabolism.
Biology, Chemistry, and Math Faculty teaching BMB elective courses and doing BMB research
Professor Cafiero’s research group uses molecular quantum mechanics to computationally study the interactions of small molecules with enzymes and DNA. The process by which small molecules find and bind to enzymes or DNA is called molecular recognition. This recognition process is dependent on the structures of both the small molecules and the enzyme or DNA macromolecules, as well as on the intermolecular forces that act between the small molecule and the macromolecules. One example of a system currently being studied is how cholesterol-lowering statin drug molecules bind to their target enzyme; this knowledge can be used to identify ways in which these statin drug molecules may be improved. Another study is focused on developing reliable models of how specific sites in DNA deform when small molecules bind between the nucleic acid base-pairs. This model would then be used to study intercalators: small molecules that are often used as chemotherapy drugs. All the systems studied share the common trait that they are strongly influenced by dispersion and induction forces between the small molecules and macromolecules.
Jonathan Fitz Gerald
One of the agriculturally significant aspects of plant growth is seed size. This is largely determined by the development of the seed endosperm. Dr. Fitz Gerald′s work focuses on the Arabidopsis gene AtFH5, a formin involved in the development of the posterior endosperm. Using a combination of molecular biology, genetics and microscopy, his aim is to understand both the role of AtFH5 in endosperm development and the pathways that regulate AtFH5 expression. Interestingly, after fertilization AtFH5 is expressed only from the maternal genome. Paternal silencing is regulated by a homologue of the animal Polycomb group complex. In animals, Polycomb complexes maintain cell identity during development. In Arabidopsis, is Polycomb maintaining male and female identity of the parental genomes? Ongoing projects include the examination of mutant plants where AtFH5 expression is altered and molecular screening for AtFH5 interacting proteins. More about Dr. Fitz Gerald′s research
Dr. Lindquester investigates mechanisms of immune evasion by herpesviruses. In collaboration with a group at St. Jude Children′s Research Hospital, he is studying the role of a protein known as interleukin 10 (IL-10) which is produced by the human pathogen, Epstein Barr virus (EBV). He is generating a recombinant murine gammaherpesvirus containing the EBV IL-10 gene to study its effects on infection, latency, and pathogenesis in a mouse animal model. More about Dr. Lindquester′s research
Laura Luque de Johnson
Dr. Luque de Johnson investigates the molecular mechanism of tight junction formation during plasmodium invasion of red blood cells. The plasmodium organism is the causal agent of Malaria, a disease of which more than 1 million people die every year and 2.5 billion people are at risk of contracting. Tight junction formation is believed to be the irreversible step in the invasion of red blood cells by the plasmodium organism. My lab focuses on EBA-175, a plasmodium surface protein believed to play a crucial role in tight junction formation. In my lab, we are characterizing the role of EBA-175 dimerization in tight junction formation. Through mutational analysis we disrupt EBA-175 dimerization and study the effects on tight junction formation and red blood cell invasion. Understanding the molecular mechanism that governs the morphological changes that take place inside the red blood cell during plasmodium invasion will improve our ability to control malaria.