2000-2001 GSC Everhart Lecture Series Speakers



Gabriel Kreiman (Biology)

Title: Imagery Neurons in the Human Brain

What we see is not necessarily what we get. The information that impinges on the retina in the eyes is transformed and modified by the nervous system through several stages of computation. There are a number of basic phenomena where there is a dissociation between our perception and retinal activation. While imagining a picture, understanding a description or recalling a route with eyes closed, most subjects report forming an image in the ``mind's eye''. Whether the neuronal processes involved in vision and imagery are the same or not has long been a matter of debate among neuroscientists, psychologists and philosophers. This phenomenon has traditionally been studied indirectly with psychological experiments, by studying the reports of patients with brain lesions or by non-invasive imaging techniques that look at the blood flow inside the brain. We have had the unique opportunity of directly recording from single neurons in humans. Subjects were epileptic patients implanted with depth electrodes for the clinical purpose of localizing the focus of the seizure for potential surgical resection. We could analyze for the first time the activity of isolated neurons in the human brain during visual imagery. We observed that there are neurons that responded to specific stimuli with the same selectivity during both vision and imagery. Therefore, this provided direct evidence for a common substrate during the processing of incoming visual information and visual recall. We also studied single neuron activity in the human brain during dreams and bistable percepts. Our studies reveal correlates at the single neuron level of the activity that goes on in our brains during the perceptual processes of vision and imagery.

Date: 30 November 2000, Thursday, 4 pm (Refreshments at 3:45)
Location: Beckman Institute Auditorium

Sujoy Mukhopadhyay (Geological and Planetary Sciences)

Title: Recovery of Life Following the Cretaceous/Tertiary Mass-Extinction Event

Two-thirds of all living species on Earth, including the dinosaurs, were suddenly wiped out 65 million years ago at the Cretaceous/Tertiary (K/T) boundary. It has been proposed that mass extinctions, like at the K/T boundary, may be driven by periodic comet showers. Although an extraterrestrial impact at the K/T boundary is widely accepted, the nature of the impactor and the global biological and climatic repercussions from this impact are debated. Alternate hypotheses put forward to explain the mass-extinctions invoke widespread volcanism or sea level changes. Resolving these hypotheses requires estimating the duration of the K/T event. Mass-extinctions due to volcanism, sea-level changes or other environmental stress factors are likely to occur over timescales of hundreds of thousands of years. On the other hand, after a catastrophic impact, the species turnover rate would be a few thousand years. Unfortunately most chronological techniques do not have sufficient resolution to date geologically instantaneous events. We use a new approach to determine the duration of such events, which also provides insight to the origin of the K/T impactor.

The Earth is constantly accreting fine-grained cosmic dust, which are deposited in sediments. Helium-3 (3He), the rare isotope of helium, is a tracer of such cosmic dust and will not record the arrival of a single large impactor. Measurements of 3He in sediments reveal a near-constant flux of cosmic dust across the K/T boundary. This observation indicates that the K/T impact was not associated with enhanced solar system dustiness and therefore not a member of a comet shower. Hence, the flux of 3He can be used to compute the sediment accumulation rate and the total duration of the K/T event. Our results show that the mass-extinction at the K/T boundary was catastrophic, ruling out volcanism and sea level changes as major players. Following the severe biotic catastrophe, life rebounded and ecosystems and food chains were restored in only 10,000 years.

Date: 1 March 2001, Thursday, 4 pm (Refreshments at 3:45)
Location: Sharp Lecture Hall, 155 Arms

Christopher Voigt (Chemical Engineering)

Title: Outrunning Nature: Optimizing In Vitro Evolution

Evolution has led to enormous diversity in the plant and animal kingdoms. The simple process of cycles of mutation and selection has fueled the intricate and complex hierarchies of chemistry in biology. Richard Dawkins referred to this process as being "blind," due to the lack of rational input from a designer. In this lecture, I will demonstrate that, while evolution is random, there is order in the types of solutions that will emerge as well as an intrinsic self-organization of the evolutionary algorithm itself. From the prospective of biotechnology, the elucidation of these dynamics will allow the design of a new generation of evolutionary methods that maximize our ability to discover novel biological molecules for pharmaceutical and industrial applications.

The in vitro evolution of enzymes presents an ideal system to study the dynamics of molecular evolution. Like natural evolution, diversity is created through mutation and recombination and the mutant enzymes are screened for improvement in desired catalytic properties (such as stability, activity, or selectivity). This simple search technique strongly resembles the genetic algorithm, a common search strategy in computer science. Theory developed to understand genetic algorithms has focused on using information about the structure of the search space to optimize evolutionary parameters (e.g., the mutation rate). Following this archetype, we first develop simple models, based on statistical mechanics, to study the gross dynamics of the evolution algorithm. Next, we apply the principles from the simple model to specific enzyme systems, through a detailed model that captures the effects of amino acid substitutions on the stability of the protein structure.

As an example of this strategy, I will describe our theoretical treatment of in vitro sexual recombination. Theory developed to understand genetic algorithms hypothesizes that the optimal crossovers are those that least disrupt structural building blocks. Based on this assumption, we have developed a computational method to predict the locations of crossovers for recombination experiments. Our predictions correlate well with crossovers that lead to functional enzymes in independent experiments with beta-lactamase, transformylase, and cytochrome P450.

Date: 6 June 2001, Wednesday, 4pm (refreshments at 3:45pm)
Location: Baxter Auditorium

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ELS Committee, els@its.caltech.edu -- revised 10 Nov 2000