CBEE Seminar with Anthony J. Kim, PhD

Date: Monday, May 18th, 2015
Time: 1:00pm - 2:00pm
Location: UC Ballroom
Title: Nanotherapeutic Strategies to Target Invasive Brain Cancer

A major limitation in the treatment of glioblastoma (GBM) and other invasive cancers is delivery of therapeutics to invading tumor cells outside of the area that is safe for surgical removal and the source of disease progression. Therefore, effective delivery to these invading cancer cells represents a promising therapeutic approach. However, achieving broad particle distribution and selective nanoparticle targeting within the brain remains a significant challenge due to the adhesive extracellular matrix (ECM) and clearance mechanisms in the brain. In this presentation, I will discuss our group’s effort in development of different therapeutic strategies to overcome these barriers toward realizing the clinical promise of nanomedicine.

2014 AEESP Distinguished Lecture Series with Dr. Bruce E. Logan , Kappe Professor of Environmental Engineering & Evan Pugh Professor, Director of Engineering Energy & Environmental Institute, Penn State University

Date: Thursday, November 13, 2014
Time: 12pm
Location: Howard University: L. K. Downing Hall, #2019 (Reading Room)

Reception to follow

Lecture 1: Microbial Fuel Technologies for Renewable Power and Biofuels Production From Waste Biomass

The ability of certain microorganisms to transfer electrons outside the cell has created opportunities for new methods of renewable energy generation based on microbial fuel cells (MFCs) that can be used to produce electrical power, microbial electrolysis cells (MECs) for transforming biologically generated electrical current into transportable fuels such as hydrogen and methane gases, as well as other devices to desalinate water or capture phosphorus. In this presentation, Dr. Logan will summarize key findings in the electromicrobiological studies of the exoelectrogenic microorganisms and communities that produce electrical current, and the electrotrophic and methanogenic communities that are used to produce hydrogen and methane gases. Recent advances will be highlighted on materials and architectures that are being developed to make these different types of METs more cost efficient, which are leading to them becoming commercially viable technologies.

Bruce Logan Professor Bruce E Logan is an Evan Pugh Professor, the Stan & Flora Kappe Professor of Environmental Engineering, and Director of the Engineering Energy & Environmental Institute at Penn State University. His current research efforts are in bioenergy production and the development of an energy sustainable water infrastructure. Dr. Logan has mentored over 110 graduate students and post docs, and is the author or co-author of over 380 refereed publications (h-index = 91) and several books. He is the founding Deputy Editor of the new ACS journal Environmental Science & Technology Letters, and a member of the US National Academy of Engineering (NAE), and a fellow of AAAS, the International Water Association (IWA), the Water Environment Federation (WEF), and the Association of Environmental Engineering & Science Professors (AEESP). Dr. Logan is a visiting professor at several universities including Newcastle University (England) and Tsinghua University (China), with ties to several other universities in Saudi Arabia, Belgium and China. He received his Ph.D. in 1986 from the University of California, Berkeley. Prior to joining the faculty at Penn State in 1997, he was on the faculty at the University of Arizona.

Co-Hosts: Howard University, Johns Hopkins University, University of Maryland College Park, University of Maryland Baltimore County

Directions and Parking: http://auxiliary.howard.edu/parking-directions-to-the-main-campus-.html

Campus Map (Downing Hall is #26): http://www.howard.edu/explore/map/

Website

For further information, please contact Kimberly Jones, kljones@howard.edu

CBEE Seminar with Dr. Corey Wilson (Yale University), Assistant Professor of Chemical & Environmental Engineering, Biomedical Engineering & Molecular Biophysics & Biochemistry

Date: Monday, September 29
Time: 12pm
Location: ITE 104

Title: Investigating Protein Structure-Function Relationships via Rational Design

Abstract: The overarching goal of the research conducted in the Wilson Research Group is to establish an integrated experimental and computational framework to translate our understanding of the fundamental principles of biophysics and biochemistry (i.e., the physicochemical properties that confer function) into useful processes, devices, therapies, and diagnostics that will benefit society. To accomplish this the Wilson Research Group focuses on two Protein Engineering approaches: (i) computational protein design and (ii) optimized strategies in protein evolution. This research program is an integrated multidisciplinary initiative that includes applied mathematics, computer science, physical chemistry, experimental protein chemistry, biochemistry, cell biology, and molecular biophysics. In turn, our ability to engineer biological materials is a rigorous test of our understanding of the structure-function relationship—on multiple time and length scales. Accordingly, this research platform holds the promise of expanding our general knowledge with regard to protein folding, molecular interactions, signal transduction and enzyme-catalyzed reactions.

CBEE is proud to announce participation in the Graduate Student Association's 36th annual Graduate Research Conference on March 26th, 2014. This event showcases graduate students and their work on our campus.

The following students will give oral presentations in Commons 332:

9:45am – Kiranmayi Mangalgiri “Photolysis of organoarsenicals in agricultural waste”

10:00am – Hilda Fadaei Khoei “The effect of activated carbon amendment on bioaccumulation of PCBs in fish”

10:15am – Adil Zuber “Two‐dimensional chromatography for applications with purification in point-of-care manufacture of therapeutic proteins”

10:30am – Ke He “Adsorption and biodegradation of fluoroquinolone antibiotics in the activated sludge treatment”

The following students will be presenting posters in UC 310:

11:00am – Sheniqua Brown “Non‐invasive glucose sensor using fluorescent labeled glucose binding protein”

11:15am – Opeyemi Ajayi “Staphylococcus aureus biofilm formation on micropatterned surfaces”

11:30am – Arundhathi Venkatasubraman “Beta‐amyloid fibrils and their interplay in Alzheimer’s disease through physico-chemical, signaling, and epigenetic mechanisms”

11:45am – Zachary Hopkins “Ozone treatment of oxybenzone: Transformation kinetics and removal of UV absorbance”

Date: Sunday, Dec. 8th, 2013

Time: 10:00 am
Location: TRC 206

Light refreshments will be served at 9:45 am

Dissertation title: Novel hybrid chromatofocusing methods for protein purification

Abstract:

The efforts made to-date to alleviate the downstream challenges faced by the biopharmaceutical industry have been mainly focused on developing novel chromatographic column packings with either higher ligand densities to accommodate larger production capacity requirements or novel ligand groups that exhibit more than one interaction mode to increase selectivity. However, despite this earlier work, there are still unexploited interactions associated with the functional groups present on the column packings that, if optimized, may lead to novel chromatographic separation techniques. Thus, the rational behind the studies investigated here is to provide innovative separation methods based on hybrid chromatofocusing techniques and employ these unexploited interactions which may be useful in protein purification process development for the biopharmaceutical industry.

A comprehensive optimization method capable of exploiting the synergetic effects both the pH and ionic strength on ion-exchange column packing has not yet been developed. Consequently, one primary research objective of this study is to establish the usefulness of employing combined pH and ionic strength gradients to obtain elements of “orthogonal” two-dimension chromatography in one ion-exchange column that is suitable for the preparative purification of proteins in both dilute and non-dilute regimes. Another main objective is to take the concepts developed in this study for ion-exchange chromatography and apply them in affinity and mixed-mode chromatography, where the ligands on the column packings may exhibit electrostatic interactions as well as hydrophobic, hydrogen bonding and/or affinity interactions, and where pH gradients play a major role in the protein adsorption/desorption process. Lastly, this work aims to increase the understanding of the technique of chromatofocusing based on the use of modern theoretical and experimental tools, and to use this understanding to develop novel hybrid chromatofocusing methods. For this purpose, the development of a computer-aided optimization methodology was also performed which allows efficient chromatographic system identification and optimized design. In this way, the computer simulation methods described here go well beyond any previous attempts at simulations in this area.

Date: Tuesday, Nov. 12th, 2013

Time: 12:00 pm

Location: TRC 206

Light refreshments will be served at 11:45 am

Dissertation title: Impact of process parameters on product titer and quality attributes during cell culture scale down

Abstract:

Quality by Design and Process Analytical Technology regulatory initiatives aim to achieve consistent production of biopharmaceutical products of predefined quality. Extensive process development studies are imperative to establish such a production process. Currently, these studies are primarily being carried out in bench scale systems. However, bench scale bioreactor studies are costly, tedious and time consuming to set up. An in-house developed, novel high-throughput minibioreactor system shows a significant potential to improve and streamline process development studies. However, in order to fully qualify this system as a scale down model, comparability between the two scales needs to be established. Comparability of product titers and product quality aspects such as glycosylation profile, which is considered to be one of the major product quality attributes, would be of greatest relevance.

Here, we investigate cell culture scale down on monoclonal antibody titers and their N-glycan profiles produced by serum free mammalian cell culture in these two systems. Methods for purification of monoclonal antibody using protein-A chromatography followed by ion exchange chromatography and N-glycan analysis using high pH anion exchange chromatography (HPAEC) with pulsed amperometric detection (PAD) were developed. Structural determination of glycans was done using MALDI TOF mass spectrometry. A comparability experiment indicated that DO (dissolved oxygen) and pH profiles, cell growth, glucose and lactate profiles were similar in bench scale bioreactors and minibioreactors. Although the relative areas of major N-glycans obtained by HPAEC were found to be comparable in two systems, antibody titers in bench scale bioreactor were about 50% higher than in minibioreactor. While investigating this, a noticeable difference in the glutamine consumption in two systems was observed. Evidence in the literature related glutamine consumption to pCO2 levels. In order to investigate the role of pCO2, a novel pCO2 sensor patch was modified for use in mammalian cell culture. This sensor revealed a difference between the pCO2 profiles in both systems. CO2 stripping studies were conducted in order to have comparable pCO2 stripping rate. A comparability study conducted at comparable pCO2 stripping rate showed similar pCO2 profiles and a significant improvement in product titers in minibioreactors was achieved. Finally, the effect of dissolved oxygen (DO) in minibioreactors and bench scale bioreactors was investigated. Effects of DO on cell growth, viability, glucose and lactate profiles, product titers and their N-glycan profiles were found to be comparable. This project attempted to understand the changes that occur during scale down in the cell culture environment, that are significant enough to impact critical process outcomes such as product titer and product quality . This understanding proved to be crucial to provide the comparability of these miniaturized systems with the bench scale systems and to establish them as a scaled down model.

Mid-Atlantic Biosolids Association and the Department of Chemical, Biochemical, and Environmental Engineering present:

The Science of Biosolids: Current Research and Implications for Management

Tuesday, November 19th, 2013

University Center Ballroom

8:00 AM - 4:00 PM

For more information and to register, visit "http://www.mabiosolids.org/index.php?page=events-calendar"

Christopher Kistler, Associate Principle Scientist for Merck

Date: Monday, October 21
Time: 12:00pm - 1:00pm
Location: TRC 206
Title: Technology Improvements to Accelerate Process Development of Biologics

Christopher Kistler, Krista Alvin, Rachel Bareither, and David Pollard
Biologics New and Enabling Technologies, Merck & Co., Inc., 126 E. Lincoln Ave, Rahway, NJ

Pressures continue to reduce the time from discovery to product launch and minimize the costs of not only manufacturing but also process development. This is particularly difficult for upstream development where large DOE designs in lab scale reactors, provides a significant equipment and resource constraint. The presentation will show how innovation through automation and single-use technology has led to more efficient process development. This includes the creation of multi use tools to handle both cell culture and microbial expression platforms. Improvements will be shown for end to end development focusing on upstream processing followed by purification and analytics. Examples include the use of cell line development automation for the elimination of manual shakeflask stages and increase throughput of clonal evaluation. For more advanced process development a novel small scale single use prototype bioreactor is evaluated. This system is designed for automated multi tank experimentation with robotic sampling, feeding and control. This is integrated with high throughput purification and analytics using a systematic approach of statistical design of experiments in combination with 'omics' technologies. This allows for a rapid end to end process development and builds a fundamental understanding of the impact of process operations to control process consistency and product quality.

Date: Friday, August 16th, 2013

Time: 10:00 am

Location: ITE 456

Light refreshments will be served at 9:45 am

Dissertation title: Proteomic Analysis of Aspergillus nidulans during Autophagy and the Role of Autophagy Genes Anatg13 and Anatg8

Abstract:

Aspergilli represent an extremely important genus of microorganisms which can be both harmful pathogens, and beneficial pharmaceutical producers. In Aspergilli’s interactions with man, suboptimal nutrient conditions are often present, and lead to a phenomenon known as autophagy. Autophagy is a cellular recycling mechanism that (in the case of macroautophagy) is augmented under nutrient limited conditions to recycle cytoplasmic macromolecules and organelles for use in essential cell functions. Strategic manipulation of autophagy could ultimately lead to improved bioprocesses or anti-fungal treatments. Using the model filamentous fungus Aspergillus nidulans, a number of important questions about autophagy have been addressed.

Critical to the study of autophagy is the balance between self-degradation and self-preservation. Therefore, we adapted an XTT metabolic activity assay for use in filamentous fungi. The assay was first tested using a number of bioprocess related stresses (e.g. temperature, shear), and found to be superior to DCW as an assessment of culture health. Next, the metabolic activity of fungal cultures was tested during autophagy inducing conditions, demonstrating that the autophagy capable TN02A3 strain was more viable than an autophagy deficient ∆atg13 strain in nutrient limiting conditions.

By analyzing the proteome of key autophagy mutants ∆Anatg13 and ∆Anatg8, an improved molecular understanding of autophagy in filamentous fungi was achieved. Using 2-dimensional electrophoresis, 44 unique proteins were observed with significant expression changes caused either by addition of rapamycin (a chemical inducer of autophagy) or deletion of Anatg13. AnAtg13 dependent changes of multiple ribosomal proteins and a key polyamine biosynthetic protein, spermidine synthase (AnSpdA), provides molecular evidence of AnAtg13 dependent lifespan extension in A. nidulans.

After establishing improved shotgun proteomic methods on the Thermo LTQ-XL, we generated a more thorough assessment of the A. nidulans response to autophagy induction by measuring protein expression as a function of time. It was found that autophagy induction caused a rapid and sustained increase in proteolysis, amino acid degradation, and lipid metabolism. These changes occurred in both the control (TN02A3) and autophagy deficient ∆Anatg8 strains. Many of the proteins with a delayed change in expression were autophagy dependent. These include proteins involved in those involved in secretion, hydrolysis of alternative carbon sources, and secondary metabolite production; all of which are important to the bioprocess industry.

Dr. Aaron Goldstein
Dept.of Chemical Engineering, Virginia Tech, Blacksburg VA

Date: Monday, April 29
Time: 12:00pm - 1:00pm
Location: ITE 456

"Fabrication of complex biomaterial scaffolds for tissue engineering by electrospinning"

The human body contains numerous orthopaedic tissues that are marked spatially gradients of mechanical properties, extracellular matrix composition, and cell phenotype. The bone-to-ligament transition, in particular, exhibits a sharp transition from a compliant fibrous tissue to a hard mineralized tissue that is critical for efficient load transmission without strain concentrations. However, such a transition is not necessarily recapitulated in surgical reconstruction of ruptured ligaments. Over the past decade, we have been interested in the micro-fiber topographies that are produced by the electrospinning process and their impact on the morphology and phenotype of adhesion-dependent mammalian cells. Initially, we began looking at whether these morphologies could be conducive to bone and ligament formation separately, and more recently we have endeavored to create electrospun materials that exhibit spatial gradients in micro-architecture, surface chemistry, and mechanical properties. This presentation will discuss fabrication methods to construct graded biomaterial scaffolds, their chemical and mechanical properties, and the in vitro culture of mesenchymal stem cells – that have the capacity to differentiate into various orthopaedic tissues – on these materials. Next, a strategy will be presented for processing these materials into large three-dimensional structures for ligament reconstruction. Finally, our ongoing efforts to incorporate biologically active factors within these electrospun materials will be described.

When: Wed. February 20, 11 am
Where: ITE 233

Engineers Without Borders - UMBC is holding a seminar on our January 2013 trip to an orphanage in Isongo, Kenya. The orphanage currently has no source for safe drinking water. On the assessment trip, the travel team collected data on the community's needs and land and water quality to help design and construct a water sanitation system.

Contact umbc.ewb@gmail.com for more information. We hope to see you there!

Dr. Desmond Lawler
Nassir I. Al-Rashid Chair in Civil Engineering
Civil, Architectural and Environmental Engineering
The University of Texas at Austin

Date: Monday, February 25, 2013
Time: 1:00pm - 2:30pm
Location: Lecture Hall 3 (101 Admin)

The Association of Environmental Engineering and Science Professors
2013 Distinguished Lecture
Presents:

Particles, Particles, and More Particles

"Particle treatment processes are at the heart of both (surface) drinking water treatment and wastewater treatment. Many contaminants in water and wastewater are particles, are made into particles, or are removed by attaching to particles. Throughout my career, I have been pursuing the links between fundamental particle properties (particularly size distributions, but also shape, surface charge, and adsorbed materials such as natural organic matter) and the optimal design and operation of particle processes. Current work includes considering the fate of nanoparticles in conventional particle processes. Flocculation, precipitation, gravity removal processes (sedimentation, flotation, thickening), granular media filtration, and dewatering have all been the focus of my work with various Master’s and Ph.D. students. In addition, we have studied the linkages of these processes to one another in conventional water treatment plants. A few of the key insights from this work include the relative insignificance of the velocity gradient in determining the success of flocculation, the importance of flow patterns in open tanks such as flocculation and sedimentation reactors, the role of detachment in the effluent water quality from granular media filters, and a design methodology for granular media filters that could save piloting costs."

Light reception to follow

For more information contact: ughosh@umbc.edu

Event co hosted by: University of Maryland Baltimore County, University of Maryland College Park, Johns Hopkins University, and Howard University

PDF Flyer

Dr. Wayne Curtis
Professor, Chemical Engineering
Pennsylvania State University

Date: Monday, February 18, 2013
Time: 12:00pm - 1:00pm
Location: ITE 456

Green (and Red) Engineering: Bioreactors to Biofuels

"Where our lab has historically focused on applied plant biotechnology, this seminar will describe the transition to a breadth of biotechnology projects that includes transplanting a hydrocarbon biosynthesis pathway from algae into a autotrophic organism that consumes H2, O2 and CO2 to produce biofuels. Our work in plant biotechnology has combined temporary immersion bioreactor systems with the delivery of embryogenic transcription factors using Agrobacterium auxotrophs toward the development of large scale plant propagation of species that are recalcitrant to somatic embryogensis (including chocolate tree). Our thin film algae bioreactors have achieved cell concentrations in excess of 20 grams per liter operating for months, and demonstrating that under light-limited conditions, algae growth is photon flux limited, and the advantage of using 'fast growing' algae is lost. Similarly, we show that for biofuel production using autotrophic growth, the energy use under non-growing conditions (maintenance energy) that is critically important for economic feasibility (not rapid growth). Our progress in genetic engineering the hydrocarbon synthesis pathway of the algae Botryococcus braunii into the autotrophic organism Rhodobacter capsulatus will be presented. Efforts to develop low-cost, low operating conditions bioreactors for biofuels will be presented along with progress on an 'engineered symbiosis' for cellulosic biofuels that combines cellulolytic capability of a obligate anaerobic organism protected by a yeast which produces fuel in exchange for oxidative protection under controlled oxygen transport rates. A few snapshots will be presented to illustrate the critical role of undergraduate research in supporting ongoing projects as well as developing new research ideas."

Edward Bouwer
Chair, Geography and Environmental Engineering
Johns Hopkins University
Baltimore, Maryland 21218

Date: Monday, January 14.
Time: 12:00 pm
Location: ITE 456.

Water Supply Challenges in the U.S.

"We take the supply of water for granted in the United States. However, there are several challenges emerging that will impact our ability to supply adequate amounts of water in the future. Some of these challenges include energy requirements for water conveyance and treatment, decaying infrastructure, influence of climate change on water availability, and the need to use waters of impaired quality. Water reuse is receiving increased attention as one strategy for meeting present and future water demand. The presence of pharmaceuticals and personal care products (PPCPs) impedes public acceptance of water recycling, which could otherwise mitigate water shortages. My laboratory is evaluating the fate of certain pharmaceuticals and personal care products (PPCPs) in model porous media. Many of the compounds studied are biodegradable at trace levels with batch cultures and in biofilms. Through a series of batch experiments, nearly all of the tested PPCPs exhibited greater than 80% biodegradation after 50 days of incubation under aerobic conditions. Additional studies examined the biodegradability of the target PPCPs at trace levels in biofilm systems. Several factors influencing the performance of biofilm reactors were tested, including influent substrate concentrations, contact time, temperature, and biofilm loss through decay. The compound removals are enhanced via secondary utilization. Overall, results from this study suggest that soil-aquifer treatment and other biofilm-based water treatment systems have great potential for effectively removing PPCPs from impacted water. "

All new graduate students need to attend UMBC and Departmental Orientation Sessions. UMBC Orientation Sessions are the week of Aug 13, and Departmental Orientation will take place the week of Aug 20, 2012.

For a schedule of both UMBC (page 1) and Departmental (page 2) Orientation activity see this link...
CBEE Department Orientation Calendar.

Bhargavi Kondragunta successfully defended her PhD today. Bhargavi preformed her research in the Moreira Lab. The title of her dissertation was "Bioprocess Convergence Using Sentinel Genes for Process Parameter Tuning."

Jose Vallejos Membreno successfully defended his PhD today. Jose preformed his research in the Rao Lab. The title of his dissertation was "Improving Upstream Bioprocessing by Enabling Process Scouting Devices with Low Cost, Disposable Oxygen and pH Sensors."

Andreia Ribeiro successfully defended her PhD today. Andreia preformed her research in the Leach Lab. The title of her dissertation was "Translating Neuronal Responses From 2D to 3D Microenvironments to Improve the Design of Biomaterials."

Miguel Acosta successfully defended his PhD today. Miguel preformed his research in the Leach Lab. The title of his dissertation was "Miniaturized probes for cell microenvironment: development, characterization, and application of fluorescent oxygen-sensing microparticles."

Goncalo Maia successfully defended his PhD today. Goncalo preformed his research in the Castellanos Lab. The title of his dissertation was "Design of Large Scale Kinetic Metabolic Models: Applications in Mammalian and Algae Metabolism."

Ben Keshet successfully defended his PhD today. Ben preformed his research in the Good Lab. The title of his dissertation was "Towards understanding the molecular details of beta amyloid neurotoxicity in Alzheimer's disease."

Jessica Schwartz successfully defended her MS today. Jessica preformed her research in the Ross lab. The title of her dissertation was "The Influence of Human Serum on Staphylococcus aureus Growth, Collagen and Fibrinogen Receptor Expression and Adhesion to Immobilized Collagen and Fibrinogen under Dynamic Shear."

Silviya Petrova Zustiak successfully defended her PhD today. Silviya preformed her research in the Leach Lab. The title of her dissertation was "Star poly(ethylene glycol) as a tunable scaffold for neural tissue engineering."

Patrick Ymele-Leki successfully defended his PhD today. Patrick preformed his research in the Ross Lab. The title of his dissertation was "Quantitative analysis of the accumulation, architectural organization, detachment and reseeding of Staphylococcus aureus biofilms under physiological fluid shear conditions."

Irina Ramos successfully defended her PhD today. Irina preformed her research in the Good Lab. The title of her dissertation was "Role of β-Amyloid Structure and residue accessibility in cell interactions associated with Alzheimer’s disease."

Dr. David Klinke, West Virginia University

DATE/TIME/LOCATION:
Monday, April 6 12:00PM, TRC, Rm 206

TITLE:
A Bayesian Perspective on Understanding Cell Signaling Pathways using Mathematical Models

ABSTRACT:
Cellular response to extracellular stimuli is governed by biochemical reactions that allow the transfer of information from the cell membrane to the nucleus and back. The integrity of this mechanism for information processing is attributed to a series of dynamic protein-protein interactions. Decades of scientific scrutiny have revealed the molecular players in many cellular signaling networks. Yet how these molecular players create a dynamic flow of information – by interacting in space, in time, and in specific systems – remains relatively unknown. Our lab focuses on combining aspects of chemical kinetics, Bayesian inference, and proteomics to quantify the functional consequences of genetic variation. The functional consequences of interest give rise to differences in the flow of information within cellular signaling pathways. Our approach will be illustrated using two examples. To provide a context for these examples, I will provide a semi-biased review the current state-of-the-art in analyzing cell signaling pathways using mathematical models. The first example focuses on understanding differences in signaling pathways among cellular models of breast cancer. The second example focuses on understanding the regulation of Interleukin-12 signaling within naïve CD4+ T cells.

Joe Piekarski successfully defended his MS today. Joe preformed his research in the Castellanos lab. The title of his dissertation was "Construction of a Dual Infection Mechanism for HIV."

Hui Guo successfully defended her MS today. Hui preformed her research in the Frey lab. The title of her dissertation was "Dispersion phenomena in micropellicular HPLC columns."

Prof. George Georgiou, PhD
Cockrell Family Regent’s Chair in Engineering #9
Department of Biomedical Engineering
Institute for Cellular and Molecular Biology
The University of Texas at Austin

Every year our department remembers our beloved former colleague, Janice Lumpkin, by sponsoring the Lumpkin Memorial Lecture, which as been presented by some of the most prominent names in biochemical engineering.

DATE/TIME/LOCATION:
UMBC's Look Ahead Conference
Wednesday, November 12, 2008
3:30 – 6:30 pm

TITLE:
Engineering the Next Generation of Protein Therapeutics

ABSTRACT:
A major long-term interest of our group is the engineering of proteins for pharmaceutical and biotechnology applications. To this end, we have developed a set of high throughput screening techniques relying on bacterial expression and flow cytometry that enable the isolation of novel proteins with desired functions from ensembles (“libraries”) of hundreds of millions of protein variants. These studies have led to the engineering of antibodies exhibiting ultra-high antigen affinity, serum and/or novel effector functions, and of therapeutic enzymes that exhibit exquisite catalytic activity and optimal pharmacological properties. Examples that will be discussed as part of this talk include:
(a) The isolation, expression and therapeutic optimization (Fc engineering) of IgG in E.coli
(b) “Humanized” non-immunogenic enzymes for amino acid depletion in cancer.
(c) Proteases that exhibit exceptional activity and selectivity towards the cleavage of desired peptide targets.

You are cordially invited to the dissertation defense of Yonghyun (John) Kim.

Date: October 10, 2008
Time: 2:00pm
Location: BIOL 004

Some refreshments will be provided.

TITLE: Proteomic Identification of Novel Regulators and Effectors of Osmoadaptaion and Autophagy of Model Filamentous Fungi Aspergillus nidulans

ABSTRACT:
The genus Aspergillus is an important grouping of filamentous fungi for study, as it contains a number of species which are either extremely helpful (e.g., in the bioprocess industry) or harmful (e.g., human/animal/crop pathogens). Here, we focus on a representative, model species, Aspergillus nidulans, and study a key cellular process called autophagy. Autophagy (more specifically, macroautophagy) is an important cellular mechanism by which cells first degrade and subsequently recycle portions of the cytosol when there is limited nutrient supply. Autophagy proteins (and regulation of their expression) are highly conserved from yeast to man, and thus our study has potentially broad implications for all eukaryotes. Currently, only a few studies exist which have characterized autophagy in fungi. To further this understanding, we employed proteomic analysis, a systems biology tool which provides a panoptic, large-scale profiling of protein expression level changes. Our broad goal here was to utilize proteomic analysis to develop a better fundamental understanding of protein expression associated with autophagy in filamentous fungi. When fully developed, this understanding may allow us to intelligently manipulate fungi at the molecular level to harness increased benefit from fungi used in the bioprocess industry and diminish detriment from pathogenic fungi.

We began by establishing one of the first, published A. nidulans proteome maps. We did this while studying osmoadaptation, which has been tied to autophagy and is a relatively well understood stress response. This study also served to validate our proteomic experimental approach. Our analysis identified a number of novel proteins that were, for the first time, linked with osmoadaptation. Next, we studied differences in protein expression patterns when A. nidulans is grown in the presence of two known inducers of autophagy, carbon starvation and rapamycin treatment. Our data suggest that some downstream effectors are shared between the rapamycin-regulated pathways and carbon-starvation regulated pathways (e.g. polar growth, cell wall degradation), that the mechanism by which they are regulated are seemingly different (e.g. 14-3-3 ArtA involved in regulating polar growth during carbon-starvation but not during rapamycin treatment), and that there are other effectors which are distinct between the two inducers (e.g. reduced amino acid biosynthesis only observed in carbon-starvation). Our final study builds on this theme by reporting the time-dependent response of an autophagy-impaired mutant (ΔAtg8) exposed to rapamycin. Our proteomic data suggest that A. nidulans, when challenged with rapamycin, upregulates gluconeogenesis, the pentose phosphate pathway, amino acid biosynthesis, secretory pathway, polarized growth, and ribosome turnover even without a fully functioning autophagy pathway. Taken together, these data imply that rapamycin-mediated effectors are distinct from those of autophagy.

James Pallikal successfully defended his MS today. James preformed his research in the Good lab. The title of his dissertation was "Investigation of MUC1 in Alzheimer's Applications."

You are all invited to attend Jessica Drew's MS thesis defense.

Date: Tuesday, July 8th
Time: 10 am
Location: ITE 227

Some refreshments will be provided, however no food is allowed in the
actual room.

Title: Application of High Throughput Bioreactors in
Subclone Selection

Abstract: The demand for monoclonal antibodies in pharmaceutical drug production
requires the highest technology be invested in obtaining a stable, high
producing cell line. Currently the most common method of selection is by
limiting dilution cloning, done in well plates. The highest producing
cell is chosen after samples from the stationary plates have been
analyzed for antibody production. The selection is based on stationary
culture, even though after scale-up cells will grow in a stirred
environment. This research investigates a way to test multiple clones in
a stirred environment by using high throughput bioreactors (HTBRs) in the
early stages of clone selection. It has been found that simply selecting
subclones based on results from stationary culture could result in the
chance of missing even higher producing clones. Instead, choosing a
clone after analyzing its performance in a stirred environment is an
improved method to select a cell line for further scale-up.

The UMBC College of Engineering and Information Technology (COEIT) invites those interested to a Pre-Commencement Breakfast and Awards Reception

Thursday May 22, 2008
8:30 to 10:30am
Engineering Building Atrium and LH5

The CBE departmental reception for our M.S. and Ph.D. graduating students, which
will be held at noon in ITE 456. The reception consists of a catered lunch, a champagne toast, and an assortment of additional entertaining activities. This event is to celebrate the accomplishments of our graduates. For pictures click here.

Ivan R. Kennedy, PhD DSc(Agric)
Director, SUNFix Centre for Nitrogen Fixation
Associate Dean (Research)
Faculty of Agriculture, Food and Natural Resources,
University of Sydney, NSW Australia

DATE/TIME/LOCATION:
Monday, May 12 12:00PM, ITE Building, Rm 227

TITLE:
Biothermodynamics for sustainability: Revisiting entropy in the form of biological action directed by DNA

ABSTRACT:
The doctrine of increasing disorder usually said to be predicted by the 2nd Law has given entropy a needlessly bad press. A more positive view of entropy relates it to the physical property of action; entropy then acts as a capacity factor indicating the distribution of energy needed to sustain the current action at a level greater than Planck’s quantum of action characteristic of zero Kelvin. We can consider life as a set of purposive action processes, dependent for its maintenance on access to specific forms of stored action potential or free energy. In this overview (which will consider entropy in all three of its thermal, statistical and action aspects) the thesis that the DNA code-script provides highly selected information needed by living organisms to ensure their survival, by directing available energy towards specific actions, will be discussed.

Anton J. Geisz, Jr. successfully defended his MS today. Anton preformed his research in the Good lab. The title of his dissertation was "Multivalent Sialtic Acid Polymers: A Novel Chemistry."

Jacob A. MGill successfully defended his MS today. Jacob preformed his research in the Castellanos lab. The title of his dissertation was "Development of an Intracellular Infection Model and Integration of Diffusional Virus Effects into a Cellular Automata Simulation."

Christopher B. Cowan successfully defended his PhD today. Christopher preformed his research in the Good lab. The title of his dissertation was "Developing Novel Materials that Capture the Alzheimer's Diseaase Associated Protein Beta Amyloid for Therapeutic & Detection Applications."

Bradford Gates successfully defended his MS today. Brad performed his research in the Castellanos lab. The title of his dissertation was "Beta Amyloid-Neuron Interactions Explored via Computational Modeling.

Derek Smith successfully defended his PhD today. Derek preformed his research in the Center for Advanced Sensing Technologies (CAST). The title of his dissertation was "Plasmonic Enhancement for the Development of High Sensitivity, Low-Cost Fluorescence Sensing With Ultrafast Detection."

Judith Kadarusman Pollack successfully defended her PhD today. Judith preformed her research in the Marten lab. The title of her dissertation was "Study of the morphology and physiology of filamentous fungi during nutrient starvation using the parallel plate flow chamber."

Michael A. Johnson successfully defended his PhD today. Michael performed his research in the Ross lab. The title of his dissertation was "Platelet-S. aureus Interactions: A Study of Thrombus Formation in Whole Blood in the Presence of Bacteria Under Physiological Shear Conditions."

Two CBE graduate students were awarded the Ph.D. in December 2007. Mike Hanson, successfully defended his dissertation, "High Throughput Bioreactor Validation and Use in Mammalian Cell Culture Process Change Studies Utilizing Gene Expression Data," (Co-Advisors Moreira and Rao). Also successfully defending was Wendy Lea, whose research topic was, "Development, Validation and Application of a Biological Antioxidant Capacity Assay using sodA::gfp as a Living Sensor" (Co-Advisors Tolosa and Rao).