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Engineering the Future of Biology and Biotechnology
As biotechnology becomes increasingly industrial in scope, the plants producing
and refining tomorrow’s fuels, textiles, plastics, and other commodities
are likely to be plants in the vegetable sense. Corn, soybeans, and even
crops of microbes will grow the materials we need. And, like today’s
chemical facilities, these literal chemical plants will be tended by chemical
engineers.
The application of chemical engineering principles to biological organisms
and processes has only become possible in the last two decades. Modern, high-performance
computing and precise, automated instrumentation powered the Human Genome
Project and continue to enable research not just into the genetic makeup
of organisms,
but into the action of proteins, the engines that drive the most basic life
functions. Armed with the data produced by genomics and proteomics investigations,
biologists can now quantitatively describe how different genes are translated
into proteins and how downstream factors impact specific biological functions.
“
Quantitation in biology used to be that someone would count the legs on a bug
and see what it was,” says C.
Sidney Burrus, prior dean of engineering at Rice
University. Biology’s newfound ability to measure and assess inputs and
outputs means that chemical engineers can harness biological components and
processes to do specific, directed work. No surprise then, that biology’s
transition from a descriptive science to an analytical and quantitative one
is redefining chemical engineering. It’s even prompted the department
at Rice to adopt an aggressive strategic plan and to change its name to the
Department of Chemical and Biomolecular Engineering.
“
Chemical engineering has traditionally comprised three foundational ‘legs’:
chemistry, physics, and math,” says Kyriacos Zygourakis, the A.J. Hartsook
Professor of Chemical and Biomolecular Engineering and department chair. “Our
new departmental mission puts molecular biology on equal footing with the field’s
foundational sciences and reflects the work chemical engineers are doing
and will do as industry seeks better, sustainable, environmentally friendly
products.”
Design, Optimize, and Control
What would a better, sustainable, environmentally friendly product
look like? You’ve probably seen (or even eaten out of) one example in the produce
refrigerators and salad bars at your local supermarket. Many of the plastic
containers used to hold cold items, such as chilled fruit and salad, are made
using NatureWorks polylactide (PLA), a polymer formed from lactic acid, which
is in turn derived by fermenting corn sugar. These “corn-tainers” offer
nearly the same utility as containers made from oil-based plastics, but
have the advantage of being completely compostable.
One of the engineers working on NatureWorks
PLA is Aristos Aristidou,
who received both his undergraduate and graduate degrees in chemical
engineering
from Rice
in the late 1980s and early 1990s. Aristidou is now leader in
quantitative physiology and fermentation within the biocatalyst development
department at NatureWorks, the business spun out of Cargill
Dow,
which originally
developed NatureWorks
PLA. He notes that producing this polymer
differs little from
traditional
chemical engineering processes used for decades in the petrochemical
and pharmaceutical industries. But the production represents
a
revolution for
the field of biotechnology.
“
We’re seeing a paradigm shift to industrial biotechnology,” Aristidou
says. “More and more of the commodities we need are going to be produced
biologically. And it’s not just an expansion in the types of products
produced—it’s also about the raw materials used. The vision is
a biorefinery concept, where you start with renewable materials and refine
them to produce not just primary products, but a range of side products, all
of which can be utilized for specific applications.” Some
of the most promising applications include specialty chemicals,
nutraceuticals,
or products
that be used as animal feed or biofertilizers. The concept, according
to Aristidou, not only results in attractive overall process
economics (industry can use
the same processes to create multiple products). but also ensures
minimum impact from the redirection of resources currently used
for food or animal
feed.
This vision, though, requires fully characterizing the processes
and systems at the heart of biology. According to Nikos Mantzaris,
assistant
professor
of chemical and biomolecular engineering at Rice, chemical
engineers are traditionally good at integrating knowledge
from sciences
aiming at understanding
the entire
process—how the components come together and work as
a cohesive system.
“
Our goal is to understand all aspects of a process using principles from math,
chemistry, physics, and, yes, biology,” says Mantzaris. “Then
our concern is how to change, improve, and control the process.
Chemical engineering
boils down to four basic objectives: analyze the entire system
and then design, optimize, and control it.”
Mantzaris points out that cells run on a complex set of chemical
reactions—and
chemical engineers deal in chemical reactions. As a result, some
of biology’s
most stubborn questions can be addressed using classic chemical
engineering principles.
Mantzaris cites research by Kathleen
Matthews, dean of the Weiss
School of Natural Sciences and Stewart Memorial Professor of
Biochemistry and Cell
Biology at Rice, as an example of how chemical engineers and
biologists can collaborate
to gain a unique and more complete understanding of biological
processes that will also facilitate the discovery and development
of new products.
Matthews
has described the function of the key protein that regulates
the expression
of the enzymes responsible for metabolizing lactose in E. coli.
“
Kathy knows exactly what to do to change properties, function and structure
of the genetic network and protein involved in the expression of the lac operon
genes,” Mantzaris says. “I don’t know how
to do this, but I can take what she knows and use it to understand
how a population
of cells
evolves in time.”
Mantzaris and colleagues at Rice hold the view that in biology,
a system isn’t
an individual cell—it’s a whole population of cells. A tumor, for
instance, is an entire population of cells gone awry. “You’re not
curing cancer in one cell, but in the whole population of cells that comprise
a tumor,” Mantzaris continues. Understanding the interaction
between single-cell dynamics and those of a population of cells
brings engineers
closer to being able to design and control precise population
behaviors.
“
Such complex questions cannot be addressed by one discipline alone. Collaboration
is the key,” Mantzaris says. An example is a collaborative
effort led by Mantzaris, which is aiming at understanding
the interplay between
genetic
networks functioning at the single-cell level and the behavior
of entire cell populations. Mantzaris and collaborators from
the departments of
biochemistry
and cell biology, bioengineering, and chemical and biomolecular
engineering received in August 2004 a five-year, $1.5-million
project funded by the
National Institute of General Medical Sciences, one of the
National Institutes of Health.
Collaborations with biologists like George
Bennett, chair
of biochemistry and cell biology at Rice University, and
Matthews also add to the
biologically based toolset available to chemical engineers.
Once engineers have
determined how a change in a specific network, like the lactose
repressor network,
can impact an entire cell population, they can suggest to
biochemists how to
manipulate
the DNA to construct original genetic networks to do specific
tasks.
“
Let’s say I want to get to a particular product,” says
Mantzaris. “The
questions chemical engineers are posing are the following.
What type of genetic network components can I put together to
do the
job? What
genes can I add or
delete to improve the process? How can I manipulate the environment
in order to maximize product formation?”
This type of thinking has been common in the development of
commodity chemicals and materials, but it’s been less
common in the development of medical therapeutics. Systematic,
systems-based
approaches to biological
processes,
though, can help scientists mediate cell growth processes
in artificial tissues, develop physiologically based pharmacokinetic
models for predicting
how drugs
and chemicals are metabolized, and engineer new drug delivery
methods.
“
The development of bioartificial tissues has been slowed, at least in part,
by an inability to quantitatively characterize and manipulate the microenvironment
of cells migrating and proliferating in large 3D scaffolds,” says Zygourakis. “Engineering
tissues with the desired function and structure means we must learn how to
maintain the nutrient concentrations and growth factors involved in cell differentiation.
It’s here that metabolic engineering and genetic networks
intersect with classical chemical engineering problems of
reaction-diffusion and
transport
phenomena.”
Implementing a New Vision
Rice has long fostered collaborations between chemical engineers
and biologists. NatureWorks’s Aristidou developed
an interest in biochemistry and biotechnology during
his junior
year at Rice
in the late 1980s. He
remembers that even then,
Rice facilitated connections between departments. After
receiving his B.S. in 1989, Aristidou worked with Bennett in biochemistry
and cell
biology and
with Ka-Yiu
San, a specialist in biochemical engineering
who now has joint appointments in bioengineering and
chemical engineering.
“
I was encouraged not just to take courses in biochemistry and cell biology,
but to partner with researchers over there to further my understanding of the
science,” Aristidou explains, noting that by learning the language and
fundamentals of biology, he’s been able to create
connections with biologists to bring engineering principles
to bear on
their research
projects.
The strategic plan for the department of chemical and
biomolecular engineering formalizes connections between
the life sciences
and chemical engineering.
The plan was developed in consultation with the department’s advisory
board, a mixture of non-Rice academics, alumni, and industrial scientists. “We
were looking forward, trying to build on what chemical engineering has been
to determine what it’s going to be decades from now,” says
Zygourakis.
The plan preserves the department’s strengths
while focusing research on areas where the department
can have
a national,
substantial impact:
developing advanced materials (catalysts, nanostructured
polymers, complex fluids, and
gas hydrates); characterizing and exploiting biosystems
to create commercial products; and making available
more affordable
and
sustainable energy
solutions.
Core undergraduate courses in energy and materials
balances, thermodynamics. transport phenomena, kinetics,
process
control, and design will
remain the same, though many courses will be revised
and new material added
to reflect
new directions in chemical engineering. Additionally,
the department has restructured the undergraduate
curriculum into four focus
areas that include
biotechnology
and environmental engineering. A biology/biotechnology
requirement is now part of the B.S. degree. The department
is even introducing
a new molecular
biology
course for engineers and a quantitative course for
modeling biological processes.
“
Engineers ask different questions about biology,” says Mantzaris. “We
like to think about the thermodynamics involved in
the TCA cycle or we notice that protein translation is ultimately
a polymerization
process.
We need a
course in which engineers can make these connections.”
The strategic plan not only builds on the department’s strengths, but
on Rice-wide expertise in nanosystems molecular biology. “Our methodological
approach, based on strong theoretical, modeling, and computational expertise,
will contribute towards changing the design principles used to develop effective
drugs, tissues with desirable structures, materials with novel properties,
and other bio-based, environmentally friendly, and sustainable technologies,” says
Zygourakis.
The department’s biological emphasis also meshes well with Rice’s
NSF-funded Center
for Biological and Environmental Nanotechnology (CBEN), established
in 2001 as the first center to focus on applications of nanotechnology to human
health and the environment. Chemical engineering researchers have been active
in CBEN since its inception, studying specific ways to control the production
and application of some of nanotechnology’s most valuable assets: single-walled
nanotubes and quantum dots. More importantly, the partnership with CBEN helps
ensure that nanotechnology applications—whether originating at Rice or
elsewhere—are introduced and maintained in a
safe, responsible manner.
“
In life science, what is quote natural and what isn’t is less clear than
in the physical sciences,” says Burrus. “In the old days, you grew
a tree and made a table. In the future, you’ll just grow the table. For
thousands of years, humans have been crudely manipulating organisms to do what
we want them to do. Now we can do it with precision. What’s special about
Rice is that we are working at every stage of this process—from
discovery to engineering to implications.”
“
We are not becoming biologists,” says Zygourakis. “We look to the
biologists to help us understand the function of key system components,” he
explains. “We come in to help them put the system to use—to find
ways to be more efficient, more safe—better.”
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