August 3, A big congratulations to Dave, who was recently promoted to Associate Professor with tenure.
A large portion of her thesis work was published in July in Scientific Reportswith a follow up paper soon to be submitted.
Tina is now off to a Senior Scientist position at Merck. The advent of engineered DNA methyltransferases MTases to target DNA methylation to specific sites in the genome Ostermeier lab papers accelerate many areas of biological research. However, targeted MTases require clear design rules to direct site-specific DNA methylation and minimize the unintended effects of off-target DNA methylation.
Multiplexing guide RNAs enabled targeting methylation to multiple sites in a single promoter and to multiple sites in multiple promoters. This programmable de novo MTase tool might be used for studying Ostermeier lab papers of initiation, spreading and inheritance of DNA methylation, and for therapeutic gene silencing.
Revolve Biotechnologies is a life science company focused on engineering better proteins using novel directed evolution technologies. The company's IP portfolio was developed in our lab.
In addition to its internal protein pipeline, Revolve is currently offering a service for construction of custom DNA variant libraries. September 27th, Earlier this month, Nirav Shelat successfully defended his thesis on engineering the herpes simplex virus thymidine kinase for enzyme prodrug therapy.
PLos ONE just published his paper on the development of a new positive genetic selection for nucleoside kinase activity in E.
July 29th, Congratulations to Tina Xiong for winning a Biotechnology Journal-sponsored poster award at the Synthetic Biology: Tina earned one of only six poster awards, and there were posters!
Survey of epistasis along an adaptive pathway June 10th, An understanding of the role of intragenic epistasis and tradeoffs in adaptation is central to an understanding of protein evolution.
Today, Journal of Molecular Biology published Barrett's extensive and systematic study of a series of fitness and epistatic landscapes along an adaptive pathway Shifting fitness and epistatic landscapes reflect trade-offs along an evolutionary pathway J.
This series of fitness and epistatic landscapes provided extensive experimental insight into the relationships between mutation, protein structure, protein stability, and epistasis and revealed the tradeoffs inherent in the evolution of new functions.
We found pervasive epistasis involving adaptive mutations that can be partially understood in terms of protein structural and stability considerations. Adaptation moved the protein to a more rugged and precarious region of the fitness landscape, which is a cost of adaptation.
When bad is good January 29, Barrett's paper Environmental changes bridge evolutionary valleys Sci.
The paper demonstrates that evolution through inferior intermediates can paradoxicaly lead to superior outcomes. Barrett subjected TEM beta-lactamase to four different selection regimen, three of which involved environmental changes that alter the fitness landscape.
The "negative selection" regimen which included steps for selection of mutations that substantially decrease antibiotic resistance outperformed the other strategies and ultimately resulted in proteins conferring the highest resistance. In the analysis of one such high resistance protein, he found that an initial, severely deleterious mutation is an initial gateway to a relatively inaccessible area of sequence space.
Furthermore, this mutation participates in higher-order positive epistasis with a number of beneficial mutations, compensating for the increasing negative epistasis between beneficial mutations as they accumulate i. The ability of "negative" selection and environmental changes to provide access to novel fitness peaks has important implications for natural evolutionary mechanisms as well as applied directed evolution.
Modular protein switches built from antibody mimetics December 7, In a just published paper in Protein Engineering Design and Selectionwe demonstrate that protein switches can be built using DARPins and monobodies as input domains.
Our manuscript describes how domain insertion can be used to create protein switches that consist of fusions between antibody mimetic proteins monobodies and DARPins and the enzyme beta-lactamase.
We demonstrate that these switches exhibit modularity in the sense that new switches can be created simply through the introduction of mutations in the antibody mimetic domain that are known to cause binding to the new ligand.
There are two significant conclusions from our work. First, it is possible to create protein switches by domain insertion using input domains that do not undergo large conformational changes upon ligand binding.
Second, DAPRins and, to a lesser extent, monobodies show promise as input domains for a modular platform for the rapid development of switches. Two recent protein switch papers October 13, Two of our papers on protein switches have recently appeared in Biotechnology and Bioengineering.
In the first paperJay Choi together with Maya Zayats from Peter Searson's lab show how an electrochemical signal can be used as an exogenous input to control protein switch function via reduction of the engineered disulfide bonds.
This study suggests that a disulfide-containing protein switch is a potentially useful platform for bioelectronic sensors with remote control of the sensing ability.
In the second paperNate Nicholes and Jen Tullman led an effort to create switches by fusing TEM-1 beta-lactamase and a variety of paralogous periplasmic binding proteins. The results indicate that the emergence of the switch property likely depends on the precise molecular details of the fusions and cannot be easily predicted from some overall general structural property of the fusion topology.Tiny Gateways with Enormous Potential Summer The molecular switches being created in Marc Ostermeier’s lab could one day target chemotherapy or .
In this Johns Hopkins engineering lab, Gurkan Guntas and Marc Ostermeier used a technique called domain insertion to join two proteins and create a molecular 'switch.' using enzymes that act like molecular scissors to cut the genes as though they were tiny strips of paper.
A second enzyme was used to re-attach these severed strips to each. Graduate Student Awards. Colin Paul from the Konstantopoulos lab received a National Science Foundation Graduate Research Fellowship..
Honorable Mentions were awarded to Barrett Steinberg and Nathan Nicholes of the Ostermeier lab and Christian Pick of the Frechette lab.
Donny Hanjaya Putra and Stephanie Fraley, PhD ’11, are Siebel Scholars. The Ostermeier lab received two new NSF grants. The aim of the first (from NSF-CBET) is to develop modular protein switches.
of CpG sites. A large portion of her thesis work was published in July in Scientific Reports, with a follow up paper soon to be submitted. Tina is now off to a Senior Scientist position at Merck.
Marc Ostermeier. Nov 18, · An essay on christmas eve song dissertation thesis on digital divide, barclays new organizational culture essay les revenants ostermeier critique essay verschil standpunt en argument essay research paper quoting titling an argumentative essay on euthanasia lumaraa dissertation, of mice and men candy characterization essay hengst dissertation gesetz der einfachen gestalt beispiel essay .
Research in the Townsend Lab is driven by fundamental interests in natural products: their chemistry, biosynthesis, combinatorial and engineered biosynthesis, enzyme mechanism, drug design and synthesis to combat infectious diseases, cancer and obesity.