The Everhart Lecture Series is a forum to encourage interdisciplinary interaction among graduate students and faculty, to share ideas about recent research developments, problems and controversies, and to recognize the exemplary presentation and research abilities of Caltech's graduate students. Lecturers discuss scientific topics at a level suitable for graduate students and faculty from all fields while addressing current research issues.
Each fall, three graduate-student lecturers are selected to present their work as part of the Everhart Lecture Series based on each student's:
Speakers receive a $500 honorarium and recognition at graduation. Streaming video recordings of previous Everhart lectures can be viewed online at the Caltech Today Theater.
Watching the Cosmic Fireworks Display: An Observer’s Log
For centuries, we have known that our dynamic Universe is adorned by cosmic fireworks: energetic and ephemeral beacons of light from a single star that are a million to a billion times brighter than our sun. Cosmic explosions have served as standard candles, uncovered dark energy, and proved that the Universe is accelerating. After living for 100 million years, a massive star dies a spectacular death where for only a few days, the site where most elements are created is illuminated.
Curiously, our knowledge of cosmic explosions has been limited only to novae and supernovae. It is an age-old conundrum that the brightest nova is 1000 times fainter than the faintest supernova; why should nature leave such a wide luminosity “gap” in-between? The simple reason is that observers have only picked the low-hanging fruit. Novae are easy to find because they are abundant. Supernovae are easy to find because they are luminous and long-lived. Empowered by recent technological advances, we designed a simple experiment that pushes the limits of previous searches: the Palomar Transient Factory.
The journey from idea to a fully commissioned factory of telescopes churning out discoveries only took three years. We recycled an old camera for an old telescope to build our discovery machine. Our real-time software pipelines process gigabytes of data in minutes to identify the relevant kilobyte to trigger a global network of telescopes.
Each telescope is charged with a single, well-defined task. The Palomar-48inch images 10,000 galaxies every night hunting for stars that weren’t there the night before. The Palomar-60inch monitors the evolution in multiple colors. The Palomar-200inch disperses the light revealing the chemical thumbprint that enables classification. Finally, the most intriguing explosions trigger a campaign spanning the entire electromagnetic spectrum – the orbiting Swift satellite for X-ray and ultraviolet, the Keck-10m telescope in Hawaii for optical and infrared, and the Expanded Very Large Array in New Mexico for radio.
And the result? In our first year of operations, we have single-handedly tripled the annual yield of cosmic explosions from all other searches. Furthermore, we are bridging the aforementioned “gap” with rare explosions, perhaps witnessing new physics – birth of black-holes, coalescing white-dwarfs and white-dwarfs collapsing into neutron-stars. We are on the brink of a paradigm shift in our understanding of stellar evolution.
Flirty, Chaste, Promiscuous: What Yeast Can Teach Us
About Controlling Cell Fate
In the last decade, cellular reprogramming has emerged as a viable therapeutic
strategy. The discovery of induced
pluripotent stem cells, the success of engineered T-cells to fight cancer, and
the burgeoning realm of RNAi strategies are fulfilling the nascent promise of
cellular reprogramming via gene therapy.
In large, these strategies rely on statically programmed levels of gene
expression to alter cellular behavior.
To construct more sophisticated programs like those found in natural
systems requires dynamic control of expression and strategies for employing
feedback. Feedback fundamentally changes
a pathway’s network topology and consequently the resultant phenotype. Endogenous MAPK networks have been shown to
alter their topology to control cell fate.
MAPK pathways regulate cellular entry into growth, differentiation, and
apoptosis, making them prime targets for control. In fact, a third of all cancers result from
improper regulation of MAPK pathways.
Establishing control of the internal signaling cascades may reinstitute
proper regulation in oncogenic cells.
Additionally, MAPK pathways direct stem cell fate. Controlling MAPK cascades is a critical step
in developing stem cell technologies for tissue engineering and the treatment
of degenerative diseases.
Recent advances in RNA-mediated control of gene expression provide both dynamic control and simple methods for implementing feedback. Paradigms have shifted in our understanding of non-coding RNAs’ (ncRNAs) ability to regulate cellular behavior. With increasing discoveries of ncRNAs that modulate gene expression, ncRNAs appear to be the defining layer of sophisticated biological control that differentiates species with remarkably similar genomes.
In this talk, I will introduce ligand-regulated ribozyme switches, a recently engineered class of ncRNAs. These switches act post-transcriptionally to destabilize transcripts in a ligand-dependent manner, thereby regulating target protein levels in response to changing ligand concentrations. I will show how engineering novel inducible networks allows for control over cellular fate in a model MAPK pathway, the Saccharomyces cerevisiae mating pathway. Specifically, I will show that within this pathway there exist titratable positive and negative regulators of pathway activity and a threshold of expression of these regulators at which cellular fate diverges. By controlling the expression of these regulators via ribozyme switches, I construct novel inducible network topologies that route cells to one of three desired fates: flirty, chaste, or promiscuous. In theory, regulation of gene expression via ribozyme switches applies to any set of promoters and genes, making this technique broadly applicable to an extensive range of endogenous networks.
Individual Particle Motion at the Microscale: A Brownian
Ballet
Understanding the micromechanics of active particles in complex fluids is
critical to some of the great technological challenges of our generation. Complex fluids encompass such diverse systems
as the interior of the cell, biofilms, and polymer networks. Gene therapy vectors, for example, rely
vitally on the motion of active, microscale particles. Uniting these problems is one fundamental
question: how do micro-particles move individually and collectively in crowded
environments? Answers to this question
hold great promise for nanotechnology and for discovery of new phenomena in
soft matter and biological physics. From
vesicle transport to ion migration, microscale objects have one feature in common:
they are continuously barraged by fluctuating thermal forces. These random forces play a central role in
particle motion; but rather than simply producing noise, random forces act
collectively to orchestrate highly coordinated motion. For example, as a motor protein drags an
organelle through the intracellular medium, its motion drives the surrounding
suspended particles out of equilibrium.
But the random Brownian motion of the background particles acts to recover
their equilibrium configuration, and collectively this gives rise to an
entropic restoring force that acts to slow the motor’s motion. Other physical processes may be present,
ranging from electrostatic to hydrodynamic to van der Waal’s interactions. Understanding the motion of such objects
requires an approach that merges continuum mechanics and statistical mechanics:
microhydrodynamics and Brownian dynamics.
Important questions include: how fast can a nano-particle move through a
cluttered suspension? Will its motion be
deterministic, or will collisions cause it to scatter and move
chaotically? What are the viscosity,
diffusivity, and osmotic pressure in such systems? Our work sets forth a framework for analyzing
the motion of active microscale particles embedded in a Brownian suspension. Through our model, active nonlinear
microrheology, we have shown that by simply tracking the motion of a particle,
one can obtain a comprehensive understanding of the overall system behavior:
viscous dissipation, diffusive and deterministic motion, and volume- and
shape-changing stresses. Previous
techniques for material interrogation were limited to bulk systems, using
techniques that ‘coarse-grain’ out the detailed motion of the particles. This opens up an entirely new regime of
systems to mechanical interrogation – and also allows the determination of an
extraordinary amount of information about complex systems by tracking the
motion of a single driven probe.
Looking for more examples? Past Everhart lectures can be found here.
Complete an application form along with a brief, sealed letter of recommendation. Letters should comment on the nominee's research and speaking skills, as well as state how long and in what capacity you have known the nominee. Feel free to nominate a graduate student regardless of whether they are presently completing an application. Self-nominations are also allowed.
Applicants must be registered Caltech graduate students at the beginning of the fall term during which they apply.
Applications must include six copies of the following:
Applications will be accepted through Friday, November 18, 2011. Top nominees will be interviewed the period of 12/12/2011 to 12/13/2011, and will be asked to present a brief (10 minute) version of their talk to a selection committee of graduate students from various fields. Final selections will be made by mid-December.
Send applications and nominations to:
Everhart Lecture Series
c/o Yun Elisabeth Wang
MC 114-96
Please email the ELS committee chair, Yun Elisabeth Wang, for inquiries.
All enrolled graduate students may apply, including those not planning to graduate this year. Applicants must have been enrolled as a Caltech graduate student at the beginning of the term during which they apply.
Sponsored by the Graduate Student Council and the Caltech Student Affairs