Eric Alani is a Professor in the Department of Molecular Biology and Genetics. Dr. Alani is a member of both the Graduate Field of Genetics, Genomics and Development and the Graduate Field of Biochemistry, Molecular and Cell Biology. The Alani lab studies roles for DNA mismatch repair proteins in maintaining genome stability.
Highly conserved mismatch repair (MMR) systems have been identified in organisms ranging from bacteria to humans that recognize and repair base pair and small insertion/deletion mismatches that arise as the result of DNA replication errors, DNA damage, and genetic recombination. In humans, mutations in MMR genes have been correlated to both an increased mutation rate and a predisposition to a hereditary form of colorectal cancer (HNPCC). HNPCC has a high cure rate if detected early, underscoring the importance of obtaining new mechanistic understandings of mismatch repair and new diagnostic tools.
My current work is focused on understanding how MMR proteins identify mismatches and signal downstream factors during DNA replication and repair, and the role of genetic background in determining the penetrance of MMR mutations. 1. We are currently analyzing the behavior of single MSH and MLH complexes interacting with DNA using total internal fluorescence microscopy. These studies are aimed at distinguishing between competing models for how MSH and MLH proteins signal downstream steps in MMR. In addition, my lab is using genetic and biochemical approaches to test interactions between MMR components and the SGS1 helicase to prevent recombination between divergent DNA sequences. 2. My group is using deep sequencing technologies to examine genome-wide mutation accumulation in wild-type and MMR mutants. This work will allow us to identify mutational hotspots in yeast and humans and provide information that should help cancer researchers distinguish mutations critical for transformation to a cancer state from those that occur after transformation. 3. We are using molecular evolution approaches to study incompatibilities in MMR. This work offers new tools to identify genetic interactions in DNA repair pathways, with the overall goal of understanding the effect of genetic background on cancer susceptibility.
My laboratory has been funded since 1995 by GM53085. A nice aspect of our current work is that it involves long-term collaborations with a single molecule biophysicist (Eric Greene, Ilya Finkelstein), and population geneticists (Charles Aquadro). The result of these efforts is a novel set of interdisciplinary approaches to study the roles of MMR in maintaining genome stability.
This section is focused on BioMG4860, Eukaryotic Genetics, a four-credit course that has been my major teaching responsibility. My other teaching commitments include or have included participating in Explorations in Undergraduate Biology (Bio101-104), mentoring in undergraduate research (BioGD499), and participating, organizing, or co-organizing Graduate Topics/Problems in Genetics and Biochemistry (BioMG7800, BioMG7810, BioMG7350), and Careers after Training in Molecular Biosciences (BioMG7800). I have also served almost every year as an Adhoc thesis reviewer in the Biology Honor Program.
BioMG4860 was created to give undergraduate and first year graduate students training in genetic analysis that builds on fundamental concepts introduced in Introductory Genetics. Concepts in BioMG4860 are presented within the context of a well-studied field, such as chromosome segregation in baker’s yeast. Genetic tools that are introduced in this context are then applied towards the study of a variety of fields such as vegetative and meiotic cell cycle control, embryonic development, and plant, population, and human genetics. My overall goal is to prepare students to independently evaluate genetic studies, to develop theories that support existing data, and to propose experimental approaches to test specific hypotheses. Students attend three hours of lecture per week, read original research papers that they then present and critically evaluate in a recitation (journal club) section, work through problem sets, and write a series of reports based on an analysis of original research articles. Students also write two in class exams and a take-home final that stress analytical approaches.
My goal in the foreseeable future is to introduce new topics that will keep the course fresh. Each year I closely examine student evaluations and then take the necessary steps to improve my teaching skills. Since 2004 all of the course material (lectures, readings, problem sets, written assignments, old exams) are available on the web through Cornell Blackboard.
A wonderful aspect of this course is that it describes a rapidly evolving field; this allows me to introduce new material and reorganize my notes on a yearly basis. Overall I am pleased with my teaching record as I feel that BioMG4860 is accessible to both undergraduate and graduate students. I have been gratified to hear from undergraduate alumni who have indicated that BioMG4860 provides an excellent preparation for their careers in basic research, medicine, and biotechnology.
For the past four years I have been lecturing in BioMG8370: PROBLEMS IN BIOCHEMISTRY, MOLECULAR AND CELL BIOLOGY. This is a class directed towards graduate students in the Field of BMCB.
Presentations and Activities
- EMBO Conference on Experimental Approaches to Evolution and Ecology. October 2014. EMBO. Heidelberg, Germany.
- Pch2 is a hexameric ring ATPase that remodels the meiotic chromosome axis protein Hop1. Canadian Society for Microbiology . June 2013. Canadian Society for Microbiology. Ottowa, Canada.
- Understanding Early Steps in DNA Mismatch Repair. Chromosome Stability. December 2012. India Institute of Science, Education and Research. Golden Peak Resort, Ponmudi Hills, Kerala India.