Events Calendar

USC Physical Sciences in Oncology Center Monthly Seminar

Speaker: Alexander Anderson, Ph.D, Senior Member Moffitt Cancer Center

Talk Title: How Do Interactions Modulate Heterogeneity In Cancer Progression and Drug Resistance?

Abstract: The proteasome controls the concentrations of most proteins in the cytosol and nucleus of eukaryotic cells. The degradation signal or degron that targets proteins for proteolysis has two components, a proteasome binding tag, usually a poly-ubiquitin chain, and an initiation site in the form of an unstructured region in the substrate. The two degron components can function in trans when separated onto two different polypeptide chains so that a ubiquitinated adaptor can target a binding partner for proteolysis. Surprisingly, the initiation region contributes significantly to the specificity of Ubiquitin-Proteasome System. The length, location and amino acid sequence of initiation sites all affect whether a protein can be degraded or not. We define these rules in model systems and show how they apply to natural proteins. Once degradation has initiated, the proteasome normally digests its substrates processively to avoid the formation of fragments with undesirable activities. Interestingly, there are a few instances where this processivity breaks down and the proteasome generates partially degraded proteins. The partial degradation is caused by stop signals in the substrate proteins and we propose that this mechanism can explain steps in some signaling pathways and may involved in some neurodegenerative diseases.

Biography: Co-director of the Integrated Mathematical Oncology (IMO) department and Senior member at Moffitt Cancer Center. Dr. Anderson performed his doctoral work on hybrid mathematical models of nematode movement in heterogeneous environments at the Scottish Crop Research Institute in Dundee, UK. His postdoctoral work was on hybrid models of tumor-induced angiogenesis with Prof. Mark Chaplain at Bath University, UK. He moved back to Dundee in 1996 where he worked for the next 12 years on developing mathematical models of many different aspects of tumor progression and treatment, including anti-angiogenesis, radiotherapy, tumor invasion, evolution of aggressive phenotypes and the role of the microenvironment. He is widely recognized as one of only a handful of mathematical oncologists that develop truly integrative models that directly impact upon biological experimentation. His pioneering work using evolutionary hybrid cellular automata models has led to new insights into the role of the tumor microenvironment in driving tumor progression. Due to his belief in the crucial role of mathematical models in cancer research he moved his group to the Moffitt Cancer Center in 2008 to establish the Integrated Mathematical Oncology department.

Host: Center for Applied Molecular Medicine

Location: Harkness Auditorium #250

Audiences: Everyone Is Invited

Contact: kristina gerber