Description:

Two PhD students from Chemical and Biological Engineerin Department will be presenting their research on Thursday, February 26th. Rachel Dudek from Leonard's Lab presenting her research titled "Engineering Cell-Based Therapies That Recognize Defined Combinations of Environmental Cues" and Mark Duncan from Miller's Lab, will be presenting "New Tools For Moving Towards Efficient Ex Vivo Platelet Production".  Detailed information is given below.

Speaker: Rachel Dudek, PhD candidate, Leonard Lab
Title: Engineering Cell-Based Therapies That Recognize Defined Combinations of Environmental Cues

Abstract
Technologies enabling bioengineers to construct cell-based therapies that sense and respond to specific environmental cues may transform our ability to design and implement novel therapeutic strategies that overcome existing barriers to treatment. To date, we lack synthetic biology “parts” that couple exclusively extracellular cues, such as protein mediators of intracellular communication, to engineered circuits comprising synthetic proteins, RNA, and/or DNA. To address this need, we are developing a suite of biosensor technologies for transducing extracellular stimuli into defined state changes within the cell. We have developed the first fully orthogonal cell surface biosensor platform, termed a modular extracellular sensor architecture (MESA). MESA comprises engineered receptors which, upon binding of a ligand stimulus, dimerize, releasing a transcription factor from the plasma membrane to regulate gene expression.

In this presentation, I will describe my work leading two areas of the development of this technology: 1) integrating novel ligand binding modalities such that one can readily engineer new receptors that recognize diverse environmental cues, and 2) engineering an intracellular gene circuit that enables the cell to “process” sensory information from multiple receptors. As a modular protein binding domain, we harnessed the camelid antibody analog termed a “nanobody”. The nanobody’s small size enables the generation of multiple nanobodies that recognize distinct, non-overlapping epitopes on a ligand of interest, and thus nanobody MESA are able to recognize monomeric or asymmetric ligand inputs. I will also discuss the design and implementation of a logical processing circuit that integrates information from MESA specific for multiple inputs to regulate gene expression based on combinatorial antigen sensing. Like many synthetic biology technologies, these biosensor platforms provide powerful tools that may be applied to scientific inquiry and investigation of disease processes as well as novel therapeutics.

Speaker: Mark Duncan, PhD candidate, Miller Lab
Title: New Tools For Moving Towards Efficient Ex Vivo Platelet Production

Abstract
Ex vivo blood cell production has been a long-standing goal of the biotechnology and hematology communities. Our lab focuses on ex vivo production of platelets due to their especially short shelf-life and the dangers of contamination that are inherent in using donated platelets. Starting with CD34+ hematopoietic stem and progenitor cells, we have generated large numbers of megakaryocytes (MKs, the precursor cell to platelets), but subsequent release of platelets from cultured MKs remains remarkably inefficient. We are thus developing new approaches to better understand (and enhance) MK commitment, expansion, and maturation from both the molecular and biophysical perspectives. In particular, we i) developed an assay for dynamically measuring key transcription factor activities during the differentiation of hematopoietic cells, providing new insights into MK commitment and maturation and, ii) developed PDMS-based microfluidic bioreactors for studying the positive effects of shear stress on accelerating platelet release. We intend to integrate the information we are learning from these studies to develop a more robust and efficient process for ex vivo platelet production.

Date & Time: Thursday, February 26th, 9:00 am - 10:00 am
Location: Abbott Auditorium, Pancoe Pavillion (refreshments will be available at 8:45 am)