Carolina Tropini
 
KC Huang’s Group


How do cells determine their shape? How do they grow? How do molecules get to the right place at the right time?
KC’s group is trying to answer these fundamental questions in biophysics using a systems biology approach.http://whatislife.stanford.edu/
 

How can organs as different as the liver and the brain arise from a single cell in the embryo? Ever since the very first embryonic division cells are able to differentiate into different cell-types, even though their genetic information is essentially identical. The key to this puzzle lies in differentially localizing proteins responsible for the activation of function-specific genes in the two daughter cells, the resulting cells will then have different behaviors. Protein localization is very often essential for development. The question are then, how is localization achieved? Can it be bypassed by some other mechanism?

There is a lot to be learned from localization, and, more interestingly, a lot more to discover. If you are interested in the topic, a good review of the field came out in Nov 09 in Science.


We use Caulobacter crescentus as a model for development; it is a bacterium that lives in fresh water and in its mature form sticks to surfaces through a stalk secreting sticky molecules which turn out to be nature’s strongest glue (that we know of so far). When it divides, the daughter cell does not have a stalk, rather it builds a flagellum that propels it away from its mother. The flagellum  is eventually shed and a new stalk is formed (a schematic of the process can be seen above in the bottom right picture). The formation and activation of the flagellum is tightly controlled by proteins, whose localization is both spatially and temporally controlled. Changing the localization gives rise to mutant cells but that can be sometimes rescued by varying other parameters. We are investigating computationally how changes in localization in the key proteins involved in this process might give rise to different phenotypes.

Understanding Protein Localization

Engineering Cell Shape through Protein Localization

Bacterial species come in a wide variety of cell shapes, the selection from which affects the localization of many intracellular components and, ultimately, cellular functions. In rod-shaped bacteria, shape determination relies on  the cytoskeleton, which is composed in part of actin and tubulin homologs such as MreB and Ftsz, respectively. These and other key proteins control the growth of the peptidoglycan cell wall, a composite of long strands of sugar molecules (glycans) cross-linked by stretchable peptides. The localization of these wall-synthesizing enzymes is highly regulated in both space and time and a systematic analysis of the links between shape and changes to localization will provide cues for the programming required to engineer bacterial cell shapes. We propose to utilize the existing protein landscape as a template for targeting proteins to new cellular loci via the method of modular scaffold design. Protein scaffolds consist of short peptide domains, which have micromolar affinities for a specific complementary ligand. We are working on co-localizing key wall-elongating proteins and other cellular components by tagging them with a scaffold and ligand domain respectively.

In the media bacteria are usually associated with diseases and unfortunately most people do not realize that they serve essential symbiotic functions in our bodies.

There are about a trillion human cells in your body. The ‘remaining’ 10 trillion are bacterial cell. With a 10:1 ratio in favor of bacterial cells one might start to realize their importance. Bacteria in our bodies help control homeostasis, digestion as well as other normal bodily functions: the lack of ‘good bacteria’ can cause numerous illnesses. Furthermore, since they are much simpler to engineer than most other cells, bacteria might  provide us with tools to create novel sources of bio-fuels as well as medical drugs.

For research purposes, bacteria are an essential workhorse to address fundamental biophysical questions as they are much simpler systems yet very similar in many aspects to our own cells.

If you want a good intro to bacteria check out this TED talk!

Why Study Bacteria?

I am studying both experimentally and computationally the importance of protein localization in model systems such as the bacteria E. coli and Caulobacter crescentus.