Editor's note: this article is by
IBM Research Staff Member Simone Bianco, PhD
nothing better on a hot day than a cold beer. Hefeweizen? Lager? Maybe a
pilsner? It’s a matter of yeast that gives all beer its flavor. Yeast is the
single-celled organism that makes an otherwise simple list of ingredients,
complex. And it’s not just for common brewing or baking. Because different
strains perform in different ways – some fermenting at high temperatures, other at cold temperatures – yeast is the one of the most-studied organisms in the world.
we were to take a look at the microscopy, we would see that these yeast strains
are morphologically different. Their internal organization differs, sometimes
dramatically. The effect of that is reflected in the way the organism performs
specific functions. In this case fermentation. A paradigm of cell biology is
that the alterations of cell morphology are connected to alterations of
chemical reactions inside the various cell structures, called organelles.
Changes in the architecture of the cell will correspond to a difference in cell
behavior, with either suppression or modification of existing cellular
capabilities, or even the emergence of new functionalities.
is, however, little mechanistic understanding of the links between cell
morphology and cell function. Evolution has provided all living organisms with
a genetic code that contains all the information necessary for each and every
cell to function properly, from single cell organisms, like yeast, to
multi-cellular, incredibly complex higher organisms like us humans.
decoding all the information contained in the genetic code is still an
impossible task, today. Tens of thousands of genes are activated at specific
times during the existence of just one yeast cell, and even more chemical
reactions will occur during its lifespan. Hundreds of protein species will
inhabit the cell, providing the building blocks of life. Monitoring this
activity is a task that cannot be tackled with today's technology. Fundamental
understanding of such an important part of the life of our cells needs a
need a new discipline: cellular engineering.
is evident that such a task cannot be accomplished by a single research
institution. Exceptional experimental capabilities need to go hand in hand with
top-of-the-line computational and analytical tools. This is why the University
of California, San Francisco, the University of California, Berkeley, Stanford
University, San Francisco State University, the San Francisco Exploratorium,
and IBM Research have joined forces. The collaboration wants to design, build,
and test models of cellular organization. And ultimately develop cells that can
perform specific functions.
of cell morphology as a proxy for cellular state and function. We can study it
through microscopy methods, which are orders of magnitude cheaper than genetic
screens, and provide enough accuracy to be used routinely in almost any
laboratory. But building relationships between morphology and functionality
requires extensively targeted experimental efforts, where cells, like beer
yeasts, need to be subject to specific stimuli, and then imaged.
the same time, it requires computational capabilities that need supercomputing-level power, and need new analysis tools to extract meaningful
information, and learn from the wealth of data that will be produced.
Furthermore, informed mathematical models are needed to quickly generate novel
hypotheses from principles of cellular organization that can be tested in the
laboratory. Finally, molecular information of a cell – its chemistry, genetics,
proteomics -- will be needed in order to generate the ontology necessary to
engineer cells that perform specific functions.
of the entire cell structure can be broken down to useable information using
techniques like PCA and LDA, then machine learning is applied to understand the
the morphology of cancer
model example of the usefulness of fundamental understanding of the connection
between cell morphology and cell behavior is cancer pathology.
a doctor suspects that a patient has a tumor, the doctor will perform a biopsy:
the removal of tissue samples of that are imaged and reviewed by a pathologist.
The doctor then relies on an extensive set of image correlations to existing
cases to compare the shape of the patient’s organelles (a cell’s wall, nucleus,
mitochondria, and other internal parts) to those imaged from tumor tissues at
different stages of progression. The correlation in the morphology becomes a
correlation in functionality: the patient’s cells, if indeed cancerous, will
replicate indefinitely, providing the hallmark behavior of any tumor.
is, in many cases, an art, and it relies on invasive techniques, the expertise
of the doctor, the state of the tumor, and different levels of understanding of
the involved cellular mechanisms. A general mechanistic understanding of the
morphological transformation processes does not yet exist, but it could
dramatically improve the efficiency of diagnosis, and even reduce the need for
invasive tests and further genetic screens. Moreover, cellular engineering
could help introduce innovative therapeutic measures, as protection of other
cells by aggregating and dividing labor between cells, or creation of new
complex organizations for novel bio-materials to protect against cancerous
perfect cell for the perfect job
is our goal with this research? If we know how cells adjust their morphology,
we could control these mechanisms, predict their performance, and increase
their range of capabilities. Engineered cells could be used to monitor the
activity of bioreactors, devices to carry out specific chemical processes in a
lab environment. NASA recently used advanced bioreactors to grow tissue samples
of liver, muscle, cartilage and bone. Scientists could soon have an endless
reservoir of tissues to test their research hypothesis, with a clear impact on
the future of bioengineering and therapeutic sciences.
disposal of organic pollutants are increasingly done by bioremediation, or
using specific enzymes to convert waste into an output that is non-toxic and
can serve another purpose within its environment. Specific detectors monitor
the production of the product to generate useful information by proper
modulation of the enzymes’ internal morphology. We can also build novel organic
toxicity sensors by sensing cells’ morphology, and understanding their
isn’t science fiction. The spirotox test estimates the toxicity of a volatile
compound, like a gas, by monitoring cell organelles’ deformation after toxic
sorts of sentinels cells, engineered to respond to changes in composition or concentration,
could also be used to prevent food adulteration and protect people from food
fraud. Or, more efficient biofuels can be engineered through reprogramming cell
morphologies to maximize the efficiency of energy production.
The hope is that, one day, we will be able to build cells
that do what we want. Even make better beer.
Labels: Almaden, cell biology, cellular engineering, materials science