BE Seminar: “Synthetic Biochemistry: Engineering Molecules and Pathways for Precision Medicine” (Michael Lin)

Save the date for the first Penn Bioengineering seminar of the fall 2021 semester! This year’s seminars will be hybrids, held virtually on zoom and live on campus!

Michael Lin, Ph.D.

Speaker: Michael Lin, Ph.D.
Associate Professor
Neurobiology, Bioengineering, and by courtesy Chemical and Systems Biology
Stanford Medicine, Stanford University

Date: Thursday, September 2, 2021
Time: 3:30-4:30 PM EDT
Zoom – check email for link or contact ksas@seas.upenn.edu
Location: Moore Room 216, 200 S. 33rd Street

Abstract: The most effective medicines are those that target the earliest causes of disease, rather than later manifestations. Engineering of biomolecules is a promising but underexplored approach to precisely detecting or targeting disease causes. I will present our work to develop a novel approach to treating cancer by detecting the signaling abnormalities that give rise to cancer. Interestingly, this effort involves biomolecular engineering at multiple scales: proteins, pathways, and viruses. I will also discuss how our work has translated serenditously to developing treatments for SARSCoV2.

Michael Lin Bio: Michael Z. Lin received an A.B. summa cum laude in Biochemistry from Harvard, an M.D. from UCLA, and a Ph.D. from Harvard Medical School. After training in biochemistry and neurobiology as a PhD student with Michael Greenberg at Harvard Medical School, Dr. Lin performed postdoctoral research in fluorescent protein engineering with Chemistry Nobel Laureate Roger Y. Tsien at UCSD. Dr. Lin is a recipient of a Burroughs Wellcome Career Award for Medical Scientists, a Rita Allen Scholar Award, a Damon Runyon-Rachleff Innovation Award, and a NIH Pioneer Award.

Seminar: “The Coming of Age of De Novo Protein Design” (David Baker)

David Baker, Ph.D.

Speaker: David Baker, Ph.D.
Professor
Biochemistry
University of Washington

Date: Thursday, March 18, 2021
Time: 3:00-4:00 PM EDT
Zoom – check email for link or contact ksas@seas.upenn.edu

Title: “The Coming of Age of De Novo Protein Design”

This seminar is jointly hosted by the Department of Bioengineering and the Department of Biochemistry & Biophysics.

Abstract:

Proteins mediate the critical processes of life and beautifully solve the challenges faced during the evolution of modern organisms. Our goal is to design a new generation of proteins that address current day problems not faced during evolution. In contrast to traditional protein engineering efforts, which have focused on modifying naturally occurring proteins, we design new proteins from scratch based on Anfinsen’s principle that proteins fold to their global free energy minimum. We compute amino acid sequences predicted to fold into proteins with new structures and functions, produce synthetic genes encoding these sequences, and characterize them experimentally. I will describe the de novo design of fluorescent proteins, membrane penetrating macrocycles, transmembrane protein channels, allosteric proteins that carry out logic operations, and self-assembling nanomaterials and polyhedra. I will also discuss the application of these methods to COVID-19 challenges.

Bio:

David Baker is the director of the Institute for Protein Design, a Howard Hughes Medical Institute Investigator, a professor of biochemistry and an adjunct professor of genome sciences, bioengineering, chemical engineering, computer science, and physics at the University of Washington. His research group is a world leader in protein design and protein structure prediction. He received his Ph.D. in biochemistry with Randy Schekman at the University of California, Berkeley, and did postdoctoral work in biophysics with David Agard at UCSF. Dr. Baker is a member of the National Academy of Sciences and the American Academy of Arts and Sciences. Dr. Baker is a recipient of the Breakthrough Prize in Life Sciences, Irving Sigal and Hans Neurath awards from the Protein Society, the Overton Prize from the ISCB, the Feynman Prize from the Foresight Institute, the AAAS Newcomb Cleveland Prize, the Sackler prize in biophysics, and the Centenary Award from the Biochemical society. He has also received awards from the National Science Foundation, the Beckman Foundation, and the Packard Foundation. Dr. Baker has published over 500 research papers, been granted over 100 patents, and co-founded 11 companies. Seventy-five of his mentees have gone on to independent faculty positions.

BE Seminar: “Multi-input Chemical Control with Computationally Designed Proteins for Research Tools and Cell Therapies” (Glenna Wink Foight)

Speaker: Glenna Wink Foight, Ph.D.
Senior Scientist
Lyell Immunopharma

Date: Thursday, February 11, 2021
Time: 3:00-4:00 PM EST
Zoom – check email for link or contact ksas@seas.upenn.edu

Title: “Multi-input Chemical Control with Computationally Designed Proteins for Research Tools and Cell Therapies”

Abstract:

Protein modules that are responsive to small molecule inputs have enabled control of cellular processes for decades’ worth of important mechanistic studies. More recently, they have gained attention as a means of control for improved safety of cellular therapies. To date, most small molecule-responsive systems have been adapted from natural proteins, which provide limited control behaviors and often rely on small molecules with non-ideal properties for use in humans. I will describe how we have used computational protein design to move beyond these naturally occurring systems to create a new set of molecular tools that are responsive to multiple clinically approved drugs. The unique architecture of our system enables more complex control behaviors for multiple cellular outputs. I will describe applications of this designed system in the control of mammalian cytoskeletal signaling, transcription, and CAR T-cell therapy.

Bio:

Dr. Glenna Foight is a Senior Scientist at Outpace Bio, where she leads a team that focuses on engineering small molecule drug-based control of cell therapies. Her work at the startups Outpace Bio and Lyell Immunopharma has involved the adaptation of technologies that she developed as a Washington Research Foundation Innovation Postdoctoral Fellow at the University of Washington. Dr. Foight received her Ph.D. in Biology from MIT and her B.S. in Biochemistry from North Carolina State University. Her background is in applying protein design and engineering to develop novel molecular interventions and control strategies for applications in basic research, cancer, and cell therapy.

BE Seminar: “Designing Biology for Detection and Control” (Pamela A. Silver)

Speaker: Pamela A. Silver, Ph.D.
Elliot T. and Onie H. Adams Professor of Biochemistry and Systems Biology
Harvard Medical School

Date: Thursday, January 28, 2021
Time: 3:00-4:00 PM EST
Zoom – check email for link or contact ksas@seas.upenn.edu

Title: “Designing Biology for Detection and Control”

Abstract:

The engineering of Biology presents infinite opportunities for therapeutic design, diagnosis, and prevention of disease. We use what we know from Nature to engineer systems with predictable behaviors. We also seek to discover new natural strategies to then re-engineer. I will present concepts and experiments that address how we approach these problems in a systematic way. Conceptually, we seek to both design cells and proteins to control disease states and to detect and predict the severity of emerging pathogens. For example, we have engineered components of the gut microbiome to act therapeutics for infectious disease, proteins to prolong cell states, living pathogen sensors and high throughput analysis to predict immune response of emerging viruses.

Bio:

Pamela Silver is the Adams Professor of Biochemistry and Systems Biology at Harvard Medical School and the Wyss Institute for Biologically Inspired Engineering. She received her BS in Chemistry and PhD in Biochemistry from the University of California. Her work has been recognized by an Established Investigator of the American Heart Association, a Research Scholar of the March of Dimes, an NSF Presidential Young Investigator Award, Claudia Adams Barr Investigator, an NIH MERIT award, the Philosophical Society Lecture, a Fellow of the Radcliffe Institute, and election to the American Academy of Arts and Sciences. She is among the top global influencers in Synthetic Biology and her work was named one of the top 10 breakthroughs by the World Economic Forum. She serves on the board of the Internationally Genetics Engineering Machines (iGEM) Competition and is member of the National Science Advisory Board for Biosecurity. She has led numerous projects for ARPA-E, iARPA and DARPA. She is the co-founder of several Biotech companies including most recently KulaBio and serves on numerous public and private advisory boards.

Penn Alumnus Peter Huwe Appointed Assistant Professor at Mercer University

Peter Huwe, Ph.D.

Peter Huwe, a University of Pennsylvania alumnus and graduate of the Radhakrishnan lab, was appointed Assistant Professor of Biomedical Sciences at the Mercer University School of Medicine beginning this summer 2020 semester.

Huwe earned dual B.S. degrees in Biology and Chemistry in 2009 from Mississippi College, where he was inducted into the Hall of Fame. At Mississippi College, Huwe had his first exposure to computational research in the laboratory of David Magers, Professor of Chemistry and Biochemistry. He went on to earn his Ph.D. in Biochemistry and Molecular Biophysics in 2014 in the laboratory of Ravi Radhakrishnan, Chair of the Bioengineering Department at Penn. As an NSF Graduate Research Fellow in Radhakrishnan’s lab, Huwe focused his research on using computational molecular modeling and simulations to elucidate the functional consequences of protein mutations associated with human diseases. Dr. Huwe then joined the structural bioinformatics laboratory Roland Dunbrack, Jr., Professor at the Fox Chase Cancer Center as a T32 post-doctoral trainee. During his post-doctoral training, Huwe held adjunct teaching appointments at Thomas Jefferson University and at the University of Pennsylvania. In 2017, Huwe became an Assistant Professor of Biology at Temple University, where he taught medical biochemistry, medical genetics, cancer biology, and several other subjects.

During each of his appointments, Huwe became increasingly more passionate about teaching, and he decided to dedicate his career to medical education. Huwe is very excited to be joining Mercer University School of Medicine as an Assistant Professor of Biomedical Sciences this summer. There, he will serve in a medical educator track, primarily teaching first and second year medical students.

“Without Ravi Radhakrishnan and Philip Rea, Professor of Biology in Penn’s School of Arts & Sciences, giving me my first teaching opportunities as a graduate guest lecturer at Penn, I may never have discovered how much I love teaching,” says Huwe. “And without the support and guidance of each of my P.I.’s [Dr.’s Magers, Radhakrishnan, and Dunbrack], I certainly would not be where I am, doing what I love.  I am incredibly thankful for all of the people who helped me in my journey to find my dream job.”

Congratulations and best of luck from everyone in Penn Bioengineering, Dr. Huwe!

Getting Physical with Developmental Biology Research

macrophages Discher
Dennis Discher, Ph.D.

By Izzy Lopez

While genetics and biochemistry research has dominated the conversation about how human bodies are formed, new research — with an old twist — is proposing that there is another star in the show of human development: mechanical forces.

At the turn of the twentieth century, medical research relied on simple mechanics to explain scientific phenomena, including how human cells morph into shape from embryo to newborn and beyond. As better chemistry techniques and DNA research burst onto the scene, however, the idea that cells could be affected by physical forces took a back seat. Now researchers are referring back to this vintage idea and bringing it into the 21st century.

Dennis Discher, Robert D. Bent Professor in the Departments of Chemical and Biomolecular Engineering, Bioengineering and Mechanical Engineering and Applied Mechanics, was featured in a recent article in Knowable Magazine for his research on the human heart and how mechanical forces exerted on heart cells give the vital organ its necessary stiffness during development.

Read the full story on the Penn Engineering blog.

New data reveals cell size sparks genome awakening in embryos

Awakening of the zygote genome over time as decreasing individual cell size triggers early embryo transcription. (Image: Hui Chen, Penn Medicine; Cell Press)

There is a transition during early development when an embryo undergoes biochemical changes, switching from being controlled by maternal molecules to being governed by its own genome.

For the first time, a team from the Perelman School of Medicine found in an embryo that activation of its genome does not happen all at once, instead it follows a specific pattern controlled primarily by the various sizes of its cells. The researchers published their results as the cover story in Developmental Cell.

In an early embryo undergoing cell division, maternally loaded RNA and proteins regulate the cell cycle. The genomes of the zygote—a term for the fertilized egg—are initially in sleep mode. However, at a point in the early life of the embryo, these zygotic nuclei “wake up” and expression from their genomes takes biochemical control over subsequent embryo development. But how an embryo “recognizes” when to undergo this transition has remained unknown.

“How an embryo ‘hands over’ control of development from mother to zygote is a fundamental question in developmental biology,” says senior author Matthew C. Good, an assistant professor of both cell and developmental biology and bioengineering. “Previously it was not appreciated that different regions of a vertebrate embryo can undergo genome activation at different times, or how directly cell size regulates the awakening of a zygote’s genome.”

Read more at Penn Medicine News.