| Start Date: | 10/17/2014 | Start Time: | 4:00 PM |
| End Date: | 10/17/2014 | End Time: | 5:30 PM |
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Event Description
Uri Hershberg, PhD, assistant professor in the School of Biomedical Engineering, Science and Health Systems and in the department of immunology and microbiology in the Drexel University College of Medicine, will discuss how, thanks to the diversity of the B-cell repertoire, the immune system can adapt to nearly any pathogen it encounters. Repertoire diversity that protects from recurrent infections helps guard against rapidly mutating pathogens and is the basis for vaccines. In the System IMmunology (SIM) lab, we combine high throughput sequencing experiments with cutting edge sequence analysis and simulation techniques to study changes in B-cell repertoire structure and diversity at rest and following immune responses. In B-cells, repertoire diversity is generated in two stages. First, a variety of B-cell receptors are encoded in the germline as gene segments, which undergo a process of random rearrangement to form the assembled receptor gene. Second, when a pathogen triggers an immune response, B-cells undergo a process of proliferation, death, and mutation of their receptor genes, leading to affinity maturation of the repertoire to the pathogen. We can thus consider the immune repertoire as a set of clonotypes each of which is a set of mutants originating in a single germline rearranged clone. To compare B-cell repertoires and consider the constraints of their evolution, we need to consider two levels of B-cell repertoire diversification and competition during the immune response: 1) clonal shift -- competition between clones, as expressed by the usage of B-cells with different germline genes, causing variation at the B-cell population level and 2) clonal drift competition between mutants from the same clone that causes sequence variation within a given clone of B-cells with the same germline origin. We have developed several methods to analyze sequence data to infer potential for change in the B-cell repertoire following affinity maturation and somatic hyper-mutation. To these methods, we have also added tools to describe the actual change in the repertoire due to these processes. Using these methods to analyze both germline and mutated repertoires combining three levels of analysis -- germline, single mutated sequence, and sets of lineage related sequences, we have shown that the process of affinity maturation is even more robust than previously considered. This is a first step in building a complex systems model of how the repertoire as a whole develops throughout a single response and through the lifetime of the organism. For more info, please visit www.biomed.drexel.edu. |
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Location:
Papadakis Integrated Sciences Building (PISB), Room 120, located at the corner of 33rd and Chestnut Streets. |
Audience:
AlumniInternational StudentsCurrent StudentsFacultyProspective StudentsPublicStaffGraduate Students |
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