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Investigators and Program Directors

image of Alain Laederach

Alain Laederach

Research Scientist, Wadsworth Center,
Computational & Structural Biology
Assistant Professor, School of Public Health, Biomedical Sciences

Ph.D., Iowa State University (2003)
Postdoctoral Fellow, Stanford University,
Genetics Department

E-mail: alain@wadsworth.org
Lab Pages: http://www.wadsworth.org/Laederach/


Folding funnel of the L-21 T. thermophila group I intron as determined by Kinfold analysis. Four major pathways lead to the folded state (three populated with Intermediates, and one direct). Three-dimensional models of the intermediates as determined by NAST, the Nucleic Acid Simulation Tool Folding funnel of the L-21 T. thermophila group I intron as determined by Kinfold analysis. Four major pathways lead to the folded state (three populated with Intermediates, and one direct). Three-dimensional models of the intermediates as determined by NAST, the Nucleic Acid Simulation Tool.

Research Interests

Generating a quantitative and predictive description of the sequence of steps leading to an assembled macromolecular complex is a contemporary challenge in the life sciences. The assembly of RNA containing macromolecular machines is a key regulatory step in fundamental cellular processes that include transcription, mRNA processing, translation, and DNA replication. With significant increases in the throughput and variety of experimental techniques that quantitatively probe assembly reactions, corresponding developments are needed in the theoretical approaches used to model these systems.

A defining characteristic of the research in the Laederach Lab is the integration of multiple kinetic, structural, and phenomenological data in dynamic and structural models of biological macromolecular assembly. Furthermore, our research aims to both develop novel computational technology as well as apply these developments to specific biological problems.

The tight integration of experiment and computation is central to our research program. We both establish new computational technology and use it to answer fundamental questions about basic molecular processes. Our work to date has focused on understanding the basic physical principles that govern RNA folding, including the role of Electrostatics, Native State Topology, tertiary contact formation, and initial conformation on the RNA folding reaction.

Our four main areas of study are:

  • Analysis and modeling of the L-21 T. thermophila intron´s folding kinetics to reveal the multiple parallel pathways in the folding reaction.
  • Structural and kinetic modeling of wild type and mutant introns under multiple solution conditions to reveal the role of initial conformation, folding conditions and tertiary contact formation hierarchy in determining molecular flux partitioning among the parallel pathways. The results of this study are illustrated in the accompanying Figure in the form of a funnel with four major folding pathways.
  • We developed and published SAFA, a semi-automated footprinting analysis software package for the quantification of gel images which is now being used in over 200 labs worldwide.
  • We developed an algorithm KinFold, for reconstructing the folding pathways and structures of intermediates of large RNAs based on local probes of molecular structure.

This work illustrates our general philosophy towards computational biology. We choose a biological problem that drives the computational research. We then develop computational tools that allow quantitative modeling and analysis so as to deepen the understanding of the process. We also identify areas where computation can contribute to the experimental aspects of the field. SAFA is an example of this approach as it allows rapid quantification of gel images and therefore eliminates a major bottleneck in the use of footprinting for RNA structural analysis.

>> Select Publications

Contact Information

Mailing Address:
Developmental Genetics and Bioinformatics
Wadsworth Center
150 New Scotland Av. Room 2003
Albany, NY 12208

Phone: (518) 486 4103
Fax: (518) 474 3181
E-mail: alain@wadsworth.org