Biology Research at IIT
Professor Howard's primary focus is on methods development in macromolecular crystallography, including software development for crystallographic data processing and synchrotron beamline robotics. As a consulting crystallographer at Southeast Regional Collaborative Access Team (SER-CAT) at the Advanced Photon Source, Argonne National Laboratory, he implements his software developments. He and his students also express, purify, crystallize, and determine the structures of proteins using crystallographic approaches. Among the structure-determination projects in his lab are studies of:
- Mutants of Vitreoscilla hemoglobin (in collaboration with Professor Ben Stark)
- Complexes between cholera toxin and its human target proteins
Spectrin-repeat constructs derived from human dystrophin (in collaboration with Professor Nick Menhart)
Vitreoscilla hemoglobin mutant Y29A in the vicinity of glutamine 53, which faces outward toward solvent in the wild-type but contacts the heme group in this mutant.
Insect Immunity and Basic Cell Biology
We are interested in the immune system of insect, which do not have antibodies or T-cells, yet are still capable of fighting off microbial infections. Better understanding of insect immunity may lead to advances in pest control and even human immunity. One project involves hemolymph (blood) coagulation in Drosophila (fruit fly) larvae, where we are testing the effects of mutations in genes we previously identified as coding for clotting factors. Goals are to learn more about the clot and its role in preventing infection. Another Project focuses on encapsulation, a cellular immune response against large foreign bodes. Capsules form in an apparent autoimmune reaction in larvae bearing mutations in the lamin gene (see figure), and we are studying how changes in gene expression lead to this response.
Finally, in collaboration with groups in Japan, Germany and Switzerland, we are analyzing the first CAGE libraries from Drosophila larvae. Each library consists of ca. 6 x 106 fragments corresponding to the first nucleotides of mRNA transcripts - Transcription Start Sites (TSSs). Identification of TTss is a vexing problem in genomics. Our work will contribute to annotation of the Drosophila genome, arguably already the best annotated genome. Multiple alternative TSSs castly increase the complexity of genome "read out", and advances in Drosophila will have implications for genomics in general, development, evolution and human health.
Improvement of bacterial strains for enhanced biodesulfurization of petroleum
Enhancement of bacterial bioenthanol production through genetic engineering with the bacterial hemoglobin gene
In our lab we use both genetic engineering and more conventional microbiology to develop bacterial strains and processes that may help improve biological removal of sulfur from petroleum and increase ethanol production from lignocellulosic materials. The latter project involves engineering to express the hemoglobin from the bacterium Vitreoscilla in a special ethanol producing strain of E. coli.
I am currently working with a number of HIV-1 investigators at the Henry Jackson Foundation in Rockville, Maryland, trying to develop applications of an algorithm that I developed at IIT, The W-Curve, for use by these investigators. It is a Pattern Recognition Algorithm used to visualize the 3-D information content of the HIV-1 Genomic Sequence. We are currently using bioinformatic techniques to correlate clinical outcomes of the virus with features seen in the W-Curves of the HIV-1 Genome.
My others areas of research include examination of unstable plasmids that encode antibiotic resistant genes in gram negative bacteria found in the intestines of poultry (funded by USA Poultry). We also were the first lab to report the discovery of the herbicide dicamba degrading gene embedded in an unstable plasmid found in a Pseudomonas strain which we latter reclassified as a Sphingomonas bacterial strain. Monsanto has patented a soybean variety that contains this gene. Soybean is now resistant to the herbicide dicamba.
Programmed Cell Death in Cancer Cells
Each year about a half millions Americans die of cancer, killing more than 1,500 people each day. The human body has 50 to 100 trillion cells. To maintain a perfect balance of cell numbers in each organ, our body has a sophisticated program, called apoptosis, to get rid of unwanted cells. Each day, many cells repair themselves or "commit suicide." If apoptosis fails to occur as it should, uncontrolled cell growth occurs, and a number of diseases can result. Apoptosis failure is a major cause of cancer.
Over the past two decades, scientists such as Jialing Xiang have taken a closer look at the stepwise apoptotic process in normal and cancer cells. Xiang is investigating the role of cellular regulator molecules involved in the signaling process. "The outcome of out research will help us to understand how cancer cells are able to escape the 'death penalty,'" she explains. "Our efforts may also identify potential cellular targets for designing anticancer drugs." Dr. Xiang's research work has been supported by the American Cancer Society and the National Institute of Health. She has published over 35 peer reviewed papers on cancer related research.