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Vertically Integrated Partners (VIP) Mentors

In 2007 there were four VIP teams led by eight faculty.  The teams focused their summer research on systems-level questions in cell systems, modeling, genomics, signal processing and evolution of complex systems.

Cell Systems:  Understanding the Cell Cycle Regulatory Network in S. cerevisiae  In this VIP project, Dr. Steven Haase (Biology) and Dr. Alex Hartemink (Computer Science) engaged team members in a study of how yeast cells regulate the many steps needed for the replication cycle.

Dr. Alex Hartemink:  “Generally, my research interests are in computational systems biology and machine learning. Specifically, my work focuses on the development and application of new statistical learning algorithms to complex problems in systems biology. Some of the research areas that interest me are mapping networks of transcriptional regulation, revealing mechanisms behind control of the eukaryotic cell cycle and improving the diagnosis and treatment of disease using high-throughput clinical data.”  

Dr. Steve Haase:  “In order to divide, cells must first duplicate their entire contents, and then segregate the duplicated contents equally into two daughter cells. The duplication and segregation events of the cell division cycle must be triggered in a strict temporal order to insure that each new daughter cell is identical to the original mother cell. Using the budding yeast, Saccharomyces cerevisiae, as a model system, we are investigating the role of a highly conserved family of cell cycle regulatory proteins, called cyclin-dependent kinases (Cdks), in maintaining the ordered sequence of events during cell division… Several lines of evidence suggest that failure to properly coordinate cell cycle events may lead to genome instability, a driving force in tumorigenesis.” 

Undergraduate members of the cell-systems VIP team in 2007 were Alexandra Balaban (Mathematics) and   Jianghai Ho (Biology).  The graduate student members were Allister Bernard (Computer Science) and   David Orlando (Bio-Genome).

Models for Genetics and Evolution of Complex Systems: Mathematical Models of Folate Mediated One-Carbon Metabolism: Two approaches  This VIP project, directed by Dr. Frederik Nijhout (Biology) and Dr. Michael Reed (Mathematics), focused on how real genes, biochemical systems and physiological systems interact to produce observed properties of living systems.  

Dr. Fred Nijhout:  “Complex traits are those whose variation is affected by many genes and environmental factors and whose inheritance does not follow Mendel’s laws. The aim of our work is to understand how genetic and developmental networks operate when there is allelic variation in their genes. This work attempts to reconstruct complex traits through mathematical models of the genetic and developmental processes by which they originate, and uses these models to study the effects of mutation and selection. Currently metabolic networks (e.g. folate metabolism) are being used to develop a deeper understanding of the functional relationships between genetic variation and trait variation, and of the mechanisms by which genetic and environmental variables interact to produce phenotypes.”

Dr. Mike Reed:  “A new research area involves the applications of mathematics to the study of various aspects of cell metabolism, in particular, folate and methionine metabolism. The folic acid cycle plays a central role in cell metabolism. Among the important functions of the folate cycle are the synthesis of pyrimidines and purines and the delivery of one carbon units to the methionine. Dietary folate deficiencies as well as mutations in enzymes of the folate cycle are associated with megaloblastic anemia, cancers of the colon, breast and cervix, affective disorders, cleft palate, neural tube defects, Alzheimer’s disease, Down's syndrome, preeclampsia and early pregnancy loss and several enzymes in the cycle are the targets of anti-cancer drugs.”  

Undergraduate members of this modeling VIP team in 2007 were Jovana Pavisic (Biology) and Russell Posner (Mathematics).  The graduate students were Tanya Kossler (Biology) and Rachel Thomas (Mathematics).

Genomics: Modeling Choice in X Chromosome Inactivation: A Mathematical Approach  In this VIP project, directed by Dr. Huntington Willard (Institute for Genome Sciences & Policy) and Dr. Lingchong You (Biomedical Engineering and Institute for Genome Sciences & Policy), students explored the dynamics of gene expression on mammalian chromosomes, both before and during the process of epigenetic silencing due to X chromosome inactivation.

 Dr. Hunt Willard:  “In female mammals, most genes on one X chromosome are silenced as a result of X-chromosome inactivation.  Previous studies have included determining the profile of X-linked genes that appear to "escape" inactivation, identifying and characterizing the X inactivation center in mouse and humans that appears to be required for inactivation to occur, and examining the cytological, genomic and chromatin patterns of epigenetic modification along the inactive X chromosome.  Mechanisms of inactivation, chromosome choice and factors responsible for the escape ability of some X genes are all issues being addressed in the Willard Lab.  A variety of approaches include in vitro studies, use of mouse models, comparative genomics between humans and lemurs, computational, and epigenetic studies.”

Dr. Lingchong You:  “Synthetic gene circuits that can precisely program cellular behavior have great potential for applications in biotechnology, computation, environmental engineering and medicine. However, constructing synthetic gene circuits with reliable, non-trivial function is extremely difficult. We use mathematical models to analyze dynamics of cellular networks, including the synthetic circuits that we are building and natural cellular networks of medical relevance. Modeling will facilitate the experimental work by guiding experimental design and by identifying design principles employed in natural systems. For cellular networks that are involved in human diseases, modeling may also identify components key to the proper function of these systems. These components may then represent potential targets for drug development.” 

Undergraduate team members of this genomics VIP team in 2007 were Stephen DeVience (Biomedical Engineering) and Chris Rowland (Biomedical Engineering).  Graduate team members were Christina Sheedy (Genetics & Genomics Program) and Yu Tanouchi (Biomedical Engineering).  

Modeling Biological Systems: Inferring Gene Regulatory Networks in Arabidopsis thaliana Root   This VIP project, directed by Dr. John Harer (Mathematics) and Dr. Philip Benfey (Biology), enabled students to investigate the gene regulatory networks in plant root development.

Dr. Benfey:  “We are using a systems biology approach to understanding cell specification. Our goal is to identify the transcriptional networks responsible for specifying all of the cells in the root. As a first step we developed a method that combines cell sorting with microarray analysis to generate the global expression pattern for every cell type in the root. From this dataset we have identified all transcription factors that are expressed in a tissue-specific pattern. We are currently localizing these transcription factors and determining their immediate targets. In collaboration with members of the Systems Biology Group at Duke we are developing computational approaches to model these transcriptional networks.”  

Dr. Harer:  Professor Harer's primary research is in the use of geometric, combinatorial and computational techniques to study a variety of problems in shape recognition, image segmentation, protein structure, root architecture and systems biology.  Among his current projects are biogeometry, systems biology and computational topology and automatic inspection in manufacturing processes.  

The undergraduate members of this modeling VIP team were Mehak Aziz (Mathematics) and Appu Kuruvilla (Undeclared).  Graduate student member was Scott Spillias (Genetics & Genomics Prgm). 

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