Much of what is known about protein dynamics has been studied using bulk biochemical techniques and chemical denaturants. By contrast, we study proteins at the single molecule level and use mechanical forces to denature proteins. Force is a ubiquitous denaturant in biology. Our results are opening new vistas into protein function and challenging some widely accepted views of protein dynamics.
Courses taught at Columbia University:
- Frontiers of Science, Science C1000
- The Biology and Physics of Single Molecules, Biology Biology W4070
- Cellular Physiology of Disease, Biology W3008/W4008
- Student evaluations: Dr. Fernandez is the BEST professor I have had a Columbia, hands down. I wish I had met him my first year here; Best Biology professor that I've ever encountered at Columbia. Very rare find! He is very clear and available for questions, and I've enjoyed going to office hours; Really wonderful teacher who genuinely wants his students to be as fascinated with the material as he is.
Research stats:153 publications, 18165 citations, h index=67 (Jan 2014)
Ambition: revolutionize protein biochemistry through the use of single molecule force-spectroscopy.
I obtained my PhD in 2012 from University of Chile (Santiago, Chile) under the supervision of Dr. Victoria Guixe, at the Biological Sciences Department. My work there was related to understanding the conformational changes that thermophilic proteins undergo in solution. We used different techniques to determine the kinetic mechanisms and biophysical properties of glycolytic enzymes from hyperthermophilic organisms.
I joined the lab in September 2012, with the intent of studying protein conformational transition but this time at single molecule level. I currently use the enzyme glucokinase as a model to study the transition triggered by ligand from the Open to the Closed conformation. Also, I am involved in several projects with different members of Professor Fernandez's lab, trying to understand the function of posttranslational modifications on folding pathways of mechanical proteins.
I carried out my MSci degree in Physics and Astronomy at the University College London. Once I graduated I moved to Grenoble (France) to do a Ph.D in applied soft matter physics given by the École Normale Supérieure (ENS) de Lyon. The research project was co-supervised by Prof. Michel Peyrard from the ENS, and Dr. Andrew Wildes from the Institute Laue-Langevin, a world leading neutron facility, where I performed most of my research. During my Ph.D I investigated the structural and dynamical properties of fibre samples made of oriented DNA molecules. The high orientation of these samples allowed us to study the dynamical fluctuations and the melting transition of DNA using neutron and X-ray scattering. Furthermore, I implemented these studies with a variety of experimental techniques such as differential scanning calorimetry in collaboration with Jean-Luc Garden and Jacques Richard from CNRS, Grenoble.
I am very interested in studying the mechanical and dynamical properties of biological phenomena, such as protein folding, from a single-molecule approach. That is why I recently became part of Fernandez’s lab as a postdoctoral researcher. My role in the lab is to lead the development of an unified physical model of the energy landscape of titin combining the genetic information and its elastic properties. The ultimate goal will be to use the model to predict the severity of diseases resulting from abnormal cellular regulation and from genetic mutations in the titin gene.
I did my PhD from Indian Institute of Chemical Biology, Kolkata under the supervision of Dr. Krishnananda Chattopadhyay. During my PhD, we showed how the ultra-fast chain dynamics of protein can be monitored at a single molecular resolution. After that, I moved to Max Planck Institute of Biochemistry and started working with Prof. Ulrich Hartl. During my postdoc in Munich, we solved the mechanism of the most important bacterial chaperonin, GroEL-GroES.
I joined the lab in March 2016, I will use force spectroscopy techniques such as magnetic tweezers and AFM to study the folding dynamics of the giant elastic muscle protein Titin and its contribution to muscle contraction. In particular, my studies will focus on the role of chaperones on promoting Titin folding and increasing the strength of a muscle contraction
I am a fifth year student in the MD/PhD program at Columbia. I graduated from Princeton University with an A.B. in Chemistry, where I did undergraduate thesis research with Dr. Michael Hecht studying the biological potentials of de novo-designed proteins. After college, I worked for Dr. J. Dirk Iglehart and Dr. J.B. Lazaro in cancer biology at the Dana Farber Cancer Institute, elucidating mechanisms of chemotherapy resistance. Since joining the Fernandez lab in Summer 2013, my research interests have focused on the determinants of mechanical stability in proteins with a particular interest in cellular adhesion structures.
I am a sixth year MD/PhD student at Columbia University. I received my undergraduate degrees in chemical engineering and chemistry from the University of Pennsylvania in 2011. While at Penn, I worked in the lab of Dr. Dennis Discher studying the effects of tissue elasticity on gene expression and stem cell differentiation. After completing two years of clinical coursework and several clinical rotations, I joined the Fernandez lab for my thesis research. I am interested in the mechanical modulation of elastic protein titin and its implications in dilated cardiomyopathy. I hope to apply techniques of single molecule force measurement to understand differential signalling of proteins in their folded and unfolded states.
Alex is a third year undergraduate student in Columbia College studying Biochemistry. He has worked on various projects with both AFM and Magnetic Tweezers, investigating the mechanical and unfolding properties of proteins. He previously worked with Dr. Kai Lao at Thermo Fisher Scientific, where he developed a novel method of on-chip DNA library preparation for Next-Generation Sequencing.
After graduation, Alex would like to attend graduate school in a life sciences field. He enjoys playing sports such as volleyball and soccer, learning about religion and philosophy, and hip-hop dancing in his free time.
Molecular Biologist and lab manager
I am in charge of the molecular biology section of the laboratory. I engineer most of the polyproteins that we use. We have a well established protocol for constructing polyproteins at the DNA level and then expressing them in bacteria. I use Talon columns and FPLC for protein purification. We struggle a bit with engineering AFM ready polyproteins. Not all of them give nice pulls. If so, I am the one that usually gets to re-engineer and/or re-express the proteins. I teach all the lab members how to do it and also I am happy to help other investigators by phone and email. I welcome inquiries.
Former postdoctoral students in tenured/tenure-track academic positions:
Ionel Popa, Ph.D.; Physics, University of Wisconsin-Milwaukee, U.S.
Jorge Alegre-Cebollada, Ph.D.; National Institute of Cardiovascular Research (CNIC), Madrid, Spain
Ronen Berkovich, Ph.D.; Chemical Engineering, Ben-Gurion University, Israel
Raul Perez-Jimenez, Ph.D.; Nanogune, San Sebastian, Spain
Sergi Garcia-Manyes, Ph.D.; Physics, Kings College London, U.K.
Jasna Brujic, Ph.D.; Physics, New York University, U.S.
Frauke Graeter, Ph.D.; Heidelberg Institute for Theoretical Studies, Germany
Sri Rama Koti Ainavarapu, Ph.D.; Chemical Sciences, Tata Institute of Fundamental Research, India
Ruchuan Liu, Ph.D.; Physics, NUS, Singapore
Robert Szoszkiewicz, Ph.D.; Physics, Kansas State University, U.S.
Hongbin Li, Ph.D.; Chemistry, University of British Columbia, Canada
Mariano Carrion Vazquez, Ph.D.; Cajal Institute, Madrid, Spain
Thomas Fisher, Ph.D.; Physiology, University of Saskatchewan, Canada
Piotr Marszalek, Ph.D.; Engineering, Duke University, U.S.
Andres Oberhauser, Ph.D.; Biochemistry & Molecular Biology, UTMB, U.S.
Brenda Farrell, Ph.D.; Department of Otolaryngology, Baylor College of Medicine, U.S.
Vladimir Parpura, MD/Ph.D.; Neurobiology, University of Alabama at Birmingham, U.S.
Keiju Okano, Ph.D.; Cell Biology, Akita Prefectural University, Japan
Iain Robinson, Ph.D.; Neurobiology, The Peninsula College of Medicine and Dentistry, U.K.
Guillermo Alvarez de Toledo, Ph.D.; Physiology & Biophysics, University of Seville, Spain
Former graduate students doing postdoctoral work:
Pallav Kosuri, PhD.; Department of Chemistry & Chemical Biology, Harvard University
Arun Wiita, MD/Ph.D.; Pharmaceutical Chemistry, UCSF.
Rodolfo Hermans, Ph.D.; London Center for Nanotechnology, U.K.
Kirstin Walther, Ph.D.; Max-Planck-Institute of Molecular Physiology, Dortmund, Germany
Former technicians studying towards a Ph.D. degree:
Georgia Squyres, Harvard University, Cambridge, MA
Diego Rojas; Teachers College, Columbia University, NY
Hector Huang; Dept. Chemistry, University of California, Berkeley, CA
Judith Latimer; Chemistry and Chemical Engineering, Caltech, CA
Shayna Busch; Math-Biology, University of Miami, FL
Wolfgang Linke, Ph.D.; Cardiovascular Physiology, Ruhr University Bochum, Germany
Carles Solsona, Ph.D.; Cell Biology, Universitat de Barcelona, Spain
Vladislav Markin, Ph.D.; Neurology and Neurotherapeutics, UT Southwestern, U.S.