Research Interests   Leave a comment

This page contains links to the various research interests in our lab, and is still under development.

PRESENT:

Physiological role of the primary cilium in homeostasis

Consider the following two parables:

The oracle of Delphi had the habit of questioning passers-by. One of the questions told the following story. I have a boat made of wooden planks. As time elapses they rot one after the other. At some time no original plank still remains in the boat: is it the same boat?

Heraclitus, you know, says that everything moves on and that nothing is at rest; and, comparing existing things to the flow of a river, he says that you could not step into the same river twice. (Plato, Cratylus 402A)

What do these have to do with my research? Both recognize an essential fact of life: all living things continually replace themselves. Each cell constantly makes new proteins to replace older copies. With few exceptions, constituent cells of organs are continually replaced via stem cells. Bones undergo continuous remodeling. Angiogenesis similarly remakes the circulatory system.

In spite of this regular turnover, most of the physical attributes of your body: your weight, temperature, blood pressure, osmolarity, etc., remain constant. Even though your body continually replenishes itself, you remain more or less the same in a physiological sense- this is the principle of homeostasis.

A couple specific examples: the endothelial cells lining your blood vessels have a fairly long life: months or years. By contrast, your entire intestinal epithelium is replaced every 5 days. The renal epithelium is replaced every couple of months or so. But note- your epithelial tissues are not sloughed off in unison like a snake shedding it’s skin!

It is hypothesized that the primary cilium is a cellular organelle that is used by cells to sense fluid flow, and that the information provided by the primary cilium is used as part of a homeostatic regulatory system. For example, combining a concentration sensor (for example, a transmembrane receptor or transporter) with a flow sensor (the cilium), results in a measurement of total amount- say total amount of salt. So, if your concentration sensor keeps your osmolarity at 300 mOsm, you can maintain your weight by keeping the total *amount* of salt constant, even though you are eating, drinking, sweating, etc.

Fuel from algae: growing gasoline

MEMS platform technology: an epithelial monolayer used as a chemical sensor

We use confluent monolayers as a model for in vivo epithelial tissue. The transepithelial resistance, current, and voltage are *very* sensitive to the health and well-being of the constituent cells: a single dead cell, once it detaches from the monolayer, reduces the transepithelial resistance from (about) 2000 Ohms to precisely 0 Ohms. Given that there are about 10^6 cells in a single monolayer, the electrical properties of the monolayer are very sensitive probes into the physiological state of the monolayer.

Thus, an electrically resistive confluent monolayer of epithelial cells represent a highly sensitive chemical sensor, for chemicals that change the physiological state of the cell- say, poisons or other toxins.

The technical challenge is to make the device simple, portable, and disposable. We have a design based on standard lithographic techniques to make a suspended membrane coupled to a microfluidic and Ag/AgCl electrodes, permitting simultaneous microscopic and electrophysiologic measurements of the membrane.

PAST:

Microscopy in Space: fluid dynamics and colloidal physics

Air-to-Ground target recognition: millimeter wave imaging, spectropolarimetry, infrared imaging, and hyperspectral imaging

Liquid Bridges: contact line dynamics, Fourier optics

Posted December 27, 2010 by resnicklab

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