Seminars

The Cecil H. and Ida Green Center for Systems Biology invites fellow scientists from other Institutions as well as from within UT Southwestern Medical Center to give seminars on the latest research. 

 

Please visit UTSW Events and filter by channel Bioinformatics to see all upcoming events.

image showing different research specialties in Green Center for Systems Biology

This Lecture Series is dedicated to highlighting the many facets of Systems Biology and its impact on biomedicine. It will feature key opinion leaders in this field and will be held four times a year.

Past Seminars

Polly Fordyce

Polly Fordyce, Ph.D.

Speaker: Polly Fordyce, Ph.D.

When: 9/13/2022 at 4 PM

Where: In-person at ND11.218

Hosted by: Kimberly Reynolds, Ph.D.

Microfluidics for high-throughput and quantitative biochemistry and biophysics

Recent technological advances in genomics and proteomics have driven an explosion in our knowledge of the molecular parts within cells. Interactions between these parts drive all biological processes: proteins bind DNA and RNA to regulate transcription and translation, dense networks of protein-protein interactions convey cellular signals, and enzyme-substrate interactions allow all of the chemical transformations essential for metabolism and signaling. The strength of these interactions predicts the timing and identity of downstream responses; therefore, quantitative biophysical and biochemical measurements are critical to decipher these networks, predict how they are disrupted in disease, and manipulate them for therapeutic purposes. In this seminar, I'll present the development of and results from several new microfluidic platforms that make it possible to acquire quantitative biochemical and biophysical data in vitro for thousands to millions of sequence variants in parallel.

 

Andreas Wagner Image

Andreas Wagner, Ph.D.

Speaker: Andreas Wagner, Ph.D.

When: 6/21/2022 at 4 PM

Where: In-person at ND11.218

Hosted by:Kimberly Reynolds, Ph.D.

Evolvability, robustness, and natural selection

Evolvability is the ability of organisms to bring forth adaptive and novel traits. Whether evolvability itself can be subject to Darwinian evolution is a fundamental question in evolutionary biology. To answer this question, we need to find out how natural selection may affect evolvability. It has been proposed that during evolution on a rugged adaptive landscape, strong selection may hinder the traversal of fitness valleys that is essential to reach high adaptive peaks. However, little experimental evidence supports this and other proposals for the role of selection in evolvability. To provide such evidence, we performed experimental evolution on light-emitting yellow fluorescent proteins. We first subjected these proteins to several generations of mutation and selection (strong or weak) for their native yellow color. We then continued evolution, but selected for the new color of green fluorescence. We found that strong selection for the old, yellow color enhanced evolvability of the new green color. To find out why, we subjected the evolving populations to high-throughput DNA sequencing, studied the evolutionary dynamics of abundant genetic variants, and examined their properties through biochemical assays. We found that strong selection enhances evolvability by increasing both mutational robustness and protein foldability. Our experiments not only demonstrate a positive role for natural selection in enhancing evolvability. They also prove that natural selection can enhance the robustness of biological systems to mutations. In doing so, selection can help a population circumnavigate rather than traverse fitness valleys. In sum, Darwinian evolution may help create the conditions necessary for its own success.

 

Timothy Mitchison. Ph.D.
Timothy Mitchison. Ph.D.

Speaker: Timothy Mitchison, Ph.D.

When: 3/8/2022 at 4 PM 

Hosted by: Gaudenz Danuser, Ph.D.

How do microtubule drugs work as medicines?

Microtubules are dynamic protein fibers that transport vesicles in non-dividing cells and chromosomes during mitosis. Small molecule drugs that target microtubules, which are mostly plant-derived toxins, are important medicines. We know how they work at the molecular level, but not how they act therapeutically in the human body. Taxanes stabilize microtubules and are used to treat adult solid cancers. They block mitosis in cancer cells, but so do more recent drug candidates that failed in the clinic, so taxanes must have additional actions. We found that taxanes, alone among anti-mitotics tested in the clinic, cause chromatin bridges in post-mitotic cells. These activate the viral DNA sensor cGAS which triggers interferon secretion and might contributes to successful tumor regression. The ancient drug colchicine destabilizes microtubules and is used at low doses to treat gout and other inflammatory diseases. Using mouse disease models, we found that colchicine acts selectively in the liver to trigger release of anti-inflammatory hepatokines. These act on circulating myeloid cells to inhibit inflammation. Our unexpected findings that both taxanes and colchicine modulate inflammatory signaling illustrates the importance of these pathways in disease and therapy and has interesting implications for drug discovery and plant-derived traditional medicines.

Please email Prapti Mody if you encounter issues joining the meeting.