CCMB Distinguished Inaugural Lectures 2005-2006
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CCMB Distinguished Lecture Series
Richard J. Roberts, Ph.D.
New England BioLabs
Restriction Enzyme and Genomes
Abstract:
With more than 300 bacterial and archaeal genomes completely sequenced and the total
sequence content of GenBank still growing exponentially, we can now gain some impression
of the distribution of RM systems in the real world. Surprisingly, these RM systems,
or the relics of them, are much more abundant than might have been guessed from
the classical biochemical screening of strains in the laboratory. In particular,
Type I systems are widely distributed in Nature and many instances of solitary specificity
subunits are found. More than 100 potential Type III and Type IV systems are found
and on average about 4 DNA methyltransferase genes are found per genome. Solitary
M genes, in which the R gene is either missing or non-functional, are much more
common than expected. However, our ability to identify M genes accurately is made
difficult by the presence of conserved motifs in genes that methylate molecules
other than DNA. Analyses of the many environmental samples in GenBank suggests that
the rate of evolution of both M and R genes is quite high and confirms previous
findings that the direct cloning of intact RM systems into E. coli is difficult
with current technology. Importantly, there is little reason to think that our current
collection of 256 Type II specificities is more than a small sample of the specificities
present in the environment.
Biography:
Dr. Richard J. Roberts is the Chief Scientific Officer at New England Biolabs, Ipswich
, Massachusetts. He was educated in England , attending the University of Sheffield
where he obtained a B.Sc. in Chemistry in 1965 and a Ph.D. in Organic Chemistry
in 1968. His postdoctoral research was carried out in Professor J. L. Strominger's
laboratory at Harvard, where he studied the tRNAs that are involved in the biosynthesis
of bacterial cell walls. From 1972 to 1992, he worked at Cold Spring Harbor Laboratory,
reaching the position of Assistant Director for Research under Dr. J. D. Watson.
He began work on the newly discovered Type II restriction enzymes in 1972 and in
the next few years more than 100 such enzymes were discovered and characterized
in Dr. Roberts' laboratory. Dr. Roberts has also been involved in studies of Adenovirus-2
and discovered split genes and mRNA splicing in 1977 for which he received the Nobel
Prize in Physiology or Medicine in1993. His laboratory sequenced the 35,937 nucleotide
Adenovirus-2 genome, and wrote some of the first programs for sequence assembly
and analysis. DNA methyltransferases are an area of active research interest and,
in collaboration with Dr. X. Cheng, DNA base flipping was discovered in 1993. Current
interests focus on the identification of restriction enzyme and methylase genes
within the GenBank database and the development of rapid methods to assay their
function.
Wednesday, May 10, 2006
4:00 - 5:00 p.m.
CIT Bldg, Room 368
115 Waterman Street
Host: Professor Sorin Istrail
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Michael Waterman, Ph.D.
University of Southern California
Whole Genome Optical Mapping
Abstract:
An innovative new technology, optical mapping, is used to infer the genome map of
the location of short sequence patterns called restriction sites. The technology,
developed by David Schwartz, allows the visualization of the maps of randomly located
single molecules around a million base pairs in length. The genome map is constructed
from overlapping these shorter maps. The mathematical and computational challenges
come from modeling the measurement errors and from the process of map assembly.
Research Interests:
I have been using computational approaches to study molecular sequence data. With
the era of genome sequencing and large-scale datasets such as from microarrays,
the importance of computational methods and bioinformatics to molecular biology
is certainly growing proportionally.
My work concentrates on the creation and application of mathematics, statistics
and computer science to molecular biology, particularly to DNA, RNA, and protein
sequence data. I am the co-developer of the Smith-Waterman algorithm for
sequence comparison and of the Lander-Waterman formulas for physical mapping and
sequencing. I am a founding editor of
Journal of Computational Biology , am on the editorial board of
seven journals, and am author of the first text in this area:
Introduction to Computational Biology: Maps, Sequences and Genomes .
Dr. Waterman is a Professor of Biological, Mathematical and Computer Sciences
at the University of Southern California . He is a Member of the National Academy
of Sciences and a Member of the French Academy of Sciences.
Friday, April 21, 2006
3:00 - 4:00 p.m.
CIT Bldg, Room 368
115 Waterman Street
Host: Professor Sorin Istrail
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Ken A Dill, Ph.D.
Department Pharmaceutical Chemistry
University of California, San Francisco
Folding Proteins by Computer: A Global Optimization Problem
Abstract:
If we could predict the structures of protein molecules using computers, it would
have great value for the discovery of new drugs. The problem is that protein molecules
have large numbers of degrees of freedom, and we need to find the single global
optimum structure in a space that grows exponentially with the length, N, of the
chain. We have explored various strategies, including methods from computational
linguistics and including new fast search methods that mimic the physics of protein
folding.
Research Interests:
Properties of Proteins. We are interested in the physical properties of proteins.
In particular, we are exploring: (1) the molecular forces that drive proteins to
fold into their biological native structures, (2) how amino acid sequences encode
those structures, (3) the thermodynamic factors that stabilize proteins against
unfolding and aggregation, and (4) the rates and mechanisms by which proteins fold.
We believe that knowledge of these physical properties can contribute to computer-based
methods for predicting protein structures, dynamics, conformational changes, and
their biological mechanisms.
Properties of Water. We are interested in the structure and physical Properties
of water. In particular, we have been developing simplified models that can be explored
analytically and through Monte Carlo computer simulations, for the properties of
pure water, for understanding hydrophobic interactions, and for ion solvation. We
believe that better understanding of water as a solvent will have value in improving
models in computational biology for the folding of proteins and RNA molecules and
for ligand docking and drug design.
CV & contact info: http://www.dillgroup.ucsf.edu/~dill/kad.html
Wednesday, March 22, 2006
4:00 - 5:00 p.m.
CIT Building
Room 368 (3rd floor)
Host: Professor Sorin Istrail
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Albert-Laszlo Barabasi
Dana Farber Cancer Institute at Harvard University, Emil T. Hofman Professor
of Physics at University of Notre Dame
Network Biology: Understanding the Cell's Functional Organization
Abstract:
Post-genomic biology requires us to move beyond the single gene description, and
understand the intricate genetic networks that mediate most cellular processes.
In the last few years we learned that cellular networks are not random, but their
structure carries the signature of self-organizing processes governed by simple
but generic laws. The analysis of the metabolic network and the protein interaction
network of several organisms indicates that, despite significant variances in their
individual components, these networks display identical topologic and scaling properties.
The hubs, highly connected nodes common in such networks, have important implications
for the cell's robustness and functionality. I will show that cellular networks
have a hierarchical architecture, allowing us to identify the organization of the
functional modules embedded in the cellular topology.
For more information see http://www.nd.edu/~alb
BIO: Albert-László Barabási, currently at the Dana Farber Cancer
Institute at Harvard University, is the Emil T. Hofman Professor of Physics at University
of Notre Dame. Educated in Bucharest and Budapest, he received a Ph.D. in physics
in 1994 from Boston University. After spending a year at IBM T.J. Watson Research
Center he joined Notre Dame in 1995. His research has lead to the discovery and
understanding of scale-free networks, capturing the structure of many complex networks
in technology and nature, from the World Wide Web to the cell. His current research
focuses on applying the concepts developed by his group for characterizing the topology
of the www and the Internet to uncovering the structural and topological properties
of complex metabolic and genetic networks. He is a Fellow of the American Physical
Society and an external member of the Hungarian Academy of Sciences. His recent
general audience book entitled Linked: The New Science of Networks (Perseus, 2002)
is available on ten languages. For more information see http://www.nd.edu/~alb.
Wednesday, January 25, 2006
4:00 - 5:00 p.m.
Lubrano Conference Room (CIT 4th Floor)
Host: Professor Sorin Istrail
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Jun Liu, Ph.D.
Department of Biostatistics
Harvard University
Cambridge MA
From Sequence Information to Gene Expression
Abstract:
Understanding how genes are regulated
in various circumstances (e.g., heatshock, starvation, etc.) is a central problem
in molecular biology. The adoption of large-scale biological data generation techniques
such as the mRNA microarrays has enabled researchers to tackle the gene regulation
problem in a global way. Using the baker's yeast as a model system, we explore the
combined use of gene upstream sequence signals to explain the observed mRNA variations
and to model the clustering effect based on multiple microarray experiments. We
will briefly discuss our methods for finding sequence signals, and our use of variable
selection techniques to screen out uninteresting ones.
Wednesday, November 30th, 2005
4:00 - 5:00 p.m.
Brown University Biomedical Center
Eddy Auditorium ~ Room 291
171 Meeting Street
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Samuel Broder, M.D.
Celera Genomics
Rockville, MD
The Human Genome: Implications for Understanding Human Biology and Medicine
Abstract:
We now live in a world in which the 3 billion letter sequence (nucleotide base pairs) of the human genome
is available as a resource for scientific discovery and medical practice. Some of the findings from
the completion of the human genome were expected, confirming knowledge presaged by many decades of
research in both human and comparative genetics. Other findings are unexpected in their scientific
and philosophical implications. In either case, the availability of the human genome is likely to
have significant implications, not only on science per se, but on how we view the human condition.
One fundamental issue is the extent to which knowledge of genomic DNA sequence defines
the evolution of our species and the essence of who we are, including the determination
of risk for illness and behavior in various settings. Should we embrace or reject
the genome in a deterministic way, believing that the human condition will ultimately
be seen entirely as a manifestation of sequence information and computation? This
talk provides reflections on what the new genomic knowledge might mean for the future
of medicine and society.
Wednesday, September 21, 2005
4:00 - 5:00 p.m.
Brown University Biomedical Center
Eddy Auditorium ~ Room 291
171 Meeting Street
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