Notes on Panel Session: MEWG
Workshop, 6 Feb 2004
Participants:
Jay Keasling
Chaitan Khosla
Michael Betenbaugh
Jacqueline Shanks
Lonnie Ingram
Peter Karp
Moderator -- Mark Segal
Each panelist was asked to
present a brief overview of the expected impacts of their work. In
addition each panelist was to address, as a roundtable, specific
questions concerning the direction ME is moving and how their work fits
in, what societal issues can be addressed by ME, what common themes are
addressed by ME research and what research emphasis should MEWG place
in its next announcement of opportunities.
Michael Betenbaugh pointed out
that ME addresses either improved yield of improved "quality" of
metabolic products in mammalian systems. By quality, he indicated that
he meant the synthesis of entirely new products from modified pathways
that could not otherwise be generated through traditional genetic
manipulations. He thought ME could address issues associated with the
cell cycle, including timing of events, and address such issues as the
cell death pathway, which is not usually included in the concept of ME.
Jay Keasling thought that better use of "omics" could be employed, and
that ME could be used to create new chemistries. Jackie Shanks believed
that the goal of an in silico plant, much as has been done for
other organisms, is a worthy one. However, ME needs to become
predictive as well as evaluative, leading to iterative hypothesis
testing. We need to model plants with secondary metabolic pathways more
complex than Arabidopsis – medicinal plants are one such
category. Shanks was interested in seeing support for quantitative
proteomics, metabolite profiling and metabolic flux analysis in plants
and other organisms. Theoretical frameworks and tools are needed for
systems analysis of biological organisms. Peter Karp was interested in
seeing genome sequences for every host of interest to ME in order to
build a robust enough data set that could be used to systematically
address the commonalities and differences of pathways. Therefore, using
the annotations from the sequencing, he would like to see modeling of
the metabolic network of these hosts. He especially wanted to see
development of enzyme genomics, the assignment of sequences to all
function, i. e. as defined by E.C. numbers. Lonnie Ingram echoed some
of what the others said and suggested we need to use ME to develop
entirely new products, taking advantage of our increasing knowledge of
biological diversity. We need more ME effort directed and unusual
organisms like extremeophiles. Chaitan Khosla also agreed with much of
what went before and added that the MEWG needed to be sure that it
catalyzed research in areas ignored by the usually funding mechanisms
of the agencies involved with ME.
When asked for comments on the
set of topics in the MEWG announcements of the past, several panelists
agreed that the topics --- instrumentation, sensors, new analytical
tools, and new experimental methods, which facilitate the study of
metabolic pathways, especially those technologies that allow the
examination of individual cells; quantitative and conceptual models
integrated with experimental studies that better characterize the
regulation and integration of complex, interacting metabolic pathways;
and the use of bioinformatics to deduce the structure, function, and
regulation of major metabolic pathways --- were not unique to metabolic
engineering. There was agreement from the panel on the "tools" that
should be developed to better address metabolic engineering problems.
In that vein, Keasling’s call for better use of "omics" tools and
Karp’s suggestion of characterizing the enzymes of hosts organisms
sequenced and used used in ME are important examples of what the tools
focus could look like. Many of the best proposals will probably combine
both cutting edge tools as applied to particular problems. However,
some proposals may be primarily tools-focused while the majority are
likely to address specific problems related to particular needs of a
specific agency.
Khosla and Betenbaugh stressed
the need to have an explicit focus on engineering new metabolic
pathways and a need to either identify entirely new problems in ME or
to develop new innovative approaches to existing ones. As the panel
noted, there are numerous important problems already being addressed
from global warming (Ingram) to feeding the world’s population (Shanks)
to health care in underdeveloped world (Khosla and Keasling) to heath
care costs in the US (Betenbaugh). A suggestion from the audience to
direct the topics of future announcements to specific societal needs
was not well received. What was clear to the panel members was that the
different mandates of the cooperating agencies and the likely
impossibility of limiting any announcement to a particular need all
could agree upon makes it very difficult to agree on specific societal
problems to address. Individual researchers will only feel qualified to
tackle specific problems.
Background on the Panel Session
