Overview
The training mission of the Molecular Biophysics Training Program (MBTP) is to produce young scientists who are equipped with the quantitative skills and physical insights required to make impactful contributions in the biological and biomedical sciences. Biophysics is increasingly making critical contributions to our understanding of biological systems especially as we gain a deeper appreciation for the complexity of such systems. Our trainees will develop the ability to think broadly about their field of research, to identify important and tractable questions, to plan experiments with care, to choose appropriate methodologies, to analyze data and results in a rigorous and quantitative manner, and to draw conclusions based on sound logic. While these abilities are generally required for all meaningful science, they are particularly critical for successful biophysicists. Our trainees will also be prepared to enter the dynamic and evolving professional fields ranging from academia, biotechnology, education, and entrepreneurship to publishing and outreach. They will be aware of the position and the role that science plays in society and will be ready to embrace responsibility and to practice equality and inclusiveness in their chosen professional fields.
MBTP will bring together biophysics trainees from two WCGS graduate bi-institutional programs: the Biochemistry & Structural Biology (BSB) program, part of the umbrella Biochemistry, Cell and Molecular Biology (BCMB) program and the Physiology, Biophysics and Systems Biology (PBSB) program. Union of the biophysics trainees in these two programs is a natural fit given that biophysics is inherently multidisciplinary – bringing together biology, chemistry, physics, computational biology, and mathematics. MBTP will provide:
- Outstanding learning and mentoring for predoctoral trainees in molecular biophysics
- World-class research opportunities
- A diverse and interactive community of students and faculty to foster scientific exchange and collaboration
- Strong foundation in performing rigorous and reproducible scientific research
- Knowledge of and exposure to various career paths for successful transition into the biomedical research workforce
Application and Eligibility
Interested students will apply to the MBTP at the end of the first year after selecting their PhD mentor, who
must be a MBTP faculty member. The admission process will include evaluation of the trainee-faculty match.
First year BSB/BCMB and PBSB Students will be exposed to MBTP faculty and their research programs via
the following mechanisms, which help recruit trainees and help ensure a good match with Program Faculty:
- All students in WCGS conduct three laboratory rotations during the first year. At the end of each rotation, the student and the PI fill out and submit a Rotation Evaluation (see appendix 3), which is submitted to WCGS. These evaluations are reviewed by the parent Program Directors to determine whether the student and the PI are a good personal and scientific match. but will also be reviewed by the MBTP co-Directors in the case of students who wish to join the MBTP.
- The PBSB program holds research lunches during which faculty presents their work to the students.
- The BCMB program holds orientation events early in the first year, during which an overview of BSB faculty is provided and faculty members present brief descriptions of their research.
- Both PBSB and BSB programs highlight their faculty during their annual retreats.
- The MBTP website (https://gradschool.weill.cornell.edu/MBTP) provides immediate access to the faculty research descriptions.
Training Activities
Training Activities
Students appointed to the training grant will be required to attend and participate in courses/activities listed below.
- Principles in Molecular Biophysics course
- MBTP Research-in-Progress seminar series
- MBTP pre-seminar journal clubs
- MBTP invitation slots to host seminar speakers
- Annual Topics in Biophysics symposium
MBTP Faculty
Faculty
Alessio Accardi
Ion channels, transporters, and lipid scramblases are integral membrane proteins that play vital roles in enabling the movement of ions, nutrients, and lipids across biological membranes. We use a combination of biophysical, structural, and bioinformatic approaches to elucidate the structural and mechanistic underpinnings of ion and lipid transport. We focus on two membrane protein families, the CLC channels and transporters and the TMEM16 channels and scramblases.
Emre Aksay
We are interested in understanding the molecular, cellular, and circuit mechanisms that give rise to the rich neural dynamics observed in the brain. Neural dynamics, the ongoing time‐varying activity patterns in populations of neurons, are critical for a wide range of motor and cognitive behaviors. To understand neural dynamics, we work at the interface between biology and physics, applying in awake animals an approach that combines molecular‐genetic manipulations, multi‐photon microscopy for stimulating and monitoring networks at the single-cell level, electrophysiology, statistical and machine learning, computational modeling, and control theory. Our efforts not only yield basic science insights into neuronal computations and how neurons interact to generate global function, but also help outline therapeutic strategies for dealing with disorders of neural dynamics.
https://physiology.med.cornell.edu/people/emre-aksay-ph-d/
Olga Boudker
We are interested in how molecular motions underly function in ion-driven membrane transporters. We employ crystallography and cryo-EM to determine transporters’ structures, single-molecule fluorescence microscopy and NMR to probe their dynamics, and bioinformatics to explore evolution. We are especially interested in transporters involved in synaptic signaling. We apply our mechanistic understanding to develop pharmacological strategies to modulate transporter activity in disease states.
Jacqueline Burré
The Burré laboratory is interested in understanding pathogenic events at the neuronal synapse that trigger neurological disorders, and to identify strategies to overcome identified deficits. Much evidence points to presynaptic terminals as initiation site for neurological diseases, where synaptic dysfunction has been shown to precede neuron death and to occur long before neuropathological symptoms become apparent. Yet, virtually nothing is known about processes involved. We currently focus on synucleins in Parkinson’s disease and other synucleinopathies, and on Munc18-1/STXBP1 and SNAP-25 in neurodevelopmental diseases including epilepsy. We employ an array of cutting-edge technologies, including biophysics, biochemistry, cell biology, imaging, and mouse models of neuropathology.
https://www.burrelab.com/wordpress/
John Chodera
Our lab uses computation and experiments to develop quantitative, multiscale models of the effects of small molecules on biomolecular macromolecules and cellular pathways. We utilize physical models and rigorous statistical mechanics to engineer novel therapeutics and tools for chemical biology and understand the physical driving forces behind the evolution of resistance mutations. We apply advanced algorithms for molecular dynamics simulations on GPUs and distributed computing platforms, in addition to robot-driven high-throughput experiments characterizing biophysical interactions between proteins and small molecules.
Jeremy Dittman
Our lab is interested in synaptic function at the molecular and circuit levels. Formation and proper function of the nervous system depend critically on the operation of chemical synapses, which are the means by which neurons transmit information to one another. We study the molecules that underlie synaptic vesicle fusion and endocytosis in C. elegans using optical, genetic, biochemical, and behavioral approaches. We are currently focused on three lines of research: spatial and temporal dynamics of synaptic proteins, the mechanisms underlying synaptic vesicle fusion and its modulation, and the impact of axonal ER on synapse function, axon integrity, and neurodegeneration.
https://sites.google.com/site/dittmanlabhomepage/
Melinda Diver
The Diver laboratory focuses on ion channels, and other membrane-embedded proteins, involved in somatosensation and pain signaling. We aim to enhance our biophysical and molecular understanding of sensory transduction and pain sensation and, specifically, how modulation of ion channels in primary afferent somatosensory neurons contributes to chronic pain. Thus, a major goal of ours is to determine mechanisms whereby tissue injury and inflammation enhance the sensitivity of primary afferent nociceptors to noxious (hyperalgesia) and innocuous (allodynia) stimuli.
www.mskcc.org/research/ski/labs/melinda-diver
David Eliezer
My lab is primarily involved with the application of NMR spectroscopy to problems in non-native structural biology. This includes characterizing the location and extent of structure in and the intermolecular interactions of aggregation-competent partially unfolded states of proteins involved in neurodegenerative disease. Specific targets include Alzheimer's Disease and Parkinson's Disease related proteins. We are also pursuing structural characterization of lipid-induced conformational changes of these proteins.
https://dae2005.wixsite.com/mysite
Richard Hite
Our research group is focused upon determining the mechanisms of intracellular ion transport with a particular focus upon the lysosome. We use a variety of structural and biophysical tools including cryo-electron microscopy, X-ray crystallography and electrophysiology to characterize these channels.
https://www.mskcc.org/research/ski/labs/richard-hite
Xin-Yun Huang
One of our research projects focuses on the structural biology of the mechanisms of activation of G-proteins by G-protein-coupled receptors (GPCRs). The signaling from GPCRs to G-proteins is one of the main signaling systems used in biology. Although we have an outline of this signaling system, the molecular bases for many steps in this signaling cascade are poorly understood. One of the pressing issues is how GPCRs activate G-proteins. Currently we use the cryo-electron microscopy, cellular and biochemical approaches to address this question.
https://physiology.med.cornell.edu/people/xin-yun-huang-ph-d/
George Khelashvili
Our overall goal of is to uncover dynamic mechanisms in fundamental biological processes of signal transduction by cell surface proteins, including G protein-coupled receptors (GPCRs), neurotransmitter:sodium-symporters, major facilitator superfamily transporters, and lipid scramblases. We use advanced quantitative methods of theoretical and computational biophysics, developed and utilized at the highest level of each specialty. We pursue interdisciplinary and multi-scale strategies integrating biophysical theory and computation with biophysical measurements and molecular cell biology experimentation.
https://physiology.med.cornell.edu/faculty/khelashvili/lab/research.html
Joshua Levitz
Membrane signaling proteins provide the molecular basis for many neurological functions and the pathophysiology of many neurological and neuropsychiatric diseases. Our lab uses high-resolution optical and chemical methods, including the development of chemical optogenetic tools and single-molecule fluorescence-based assays, to elucidate the fundamental biophysical processes that drive receptor function. We aim to gain a deeper understanding of the role of individual receptors and downstream effectors in synapse function and disease.
Christopher Lima
We are a basic research laboratory that studies the structural, biochemical, and functional basis for macromolecules involved in post-translational protein modification by ubiquitin and ubiquitin-like proteins including SUMO, and pathways that contribute to co- and post-transcriptional RNA maturation, processing and decay.
https://www.mskcc.org/research/ski/labs/christopher-lima
Stephen Long
Our laboratory uses a combination of cryo-electron microscopy, x-ray crystallography, and functional approaches to study the mechanisms of eukaryotic ion channels involved in calcium signaling and membrane-embedded enzymes.
https://www.mskcc.org/research/ski/labs/stephen-long
Anant Menon
We are interested in fundamental aspects of cellular membrane biogenesis. Our work covers a number of areas concerned with lipid biosynthesis, propagation of the phospholipid bilayer of biological membranes, translocation (flip-flop) of lipids across bilayers, and intracellular lipid transport. We approach these problems through biochemical, biophysical, genetic and chemical methods.
We measure our success by the high quality of the research publications we generate and whether our students and postdocs have successful careers. Our first goal is to maintain a creative and innovative research environment with high standards and rigor in the planning and execution of experiments, in data analysis, and in publications. Our second goal - of equal importance - is to prepare graduate students and postdocs for careers in academia and biotech. We strongly believe that research leaders of the future must be able not only to be creative, willing to learn new methods, and be excellent experimentalists or computational scientists, but must also master how to work in an interdisciplinary, diverse, and collaborative research environment.
Dimitar Nikolov
We are interested in understanding how receptors located on the surface of developing axons and neurons interact with extracellular ligands to guide the development of the nervous system and the wiring of the brain. In our investigations, we use X-ray crystallography combined with other biophysical, biochemical, and cell biological approaches. Some of the ligand/receptor signaling systems that we currently study include ephrins/Eph receptors, netrins/DCC/Unc5, NogoR/Nogo and angiopoietins/Ties. Recently we also became interested in how henipaviruses interact and fuse with target cells.
https://www.mskcc.org/research/ski/labs/dimitar-nikolov
Crina Nimigean
Research in our laboratory is geared toward understanding how ion channel protein structure and mechanism interrelate at the molecular level to allow channels to elaborate various biological properties. We use a combination of structural, biochemical, and electrophysiological approaches to evaluate fundamental channel properties.
Lawrence Palmer
The kidney precisely controls the levels of electrolytes in the plasma. This function is vital, as the body requires a constant internal milieu to function properly. Our laboratory is interested in the cellular and molecular events involved in the transport of Na+ and K+ between blood and urine, and in the hormonal mechanisms underlying the regulation of these transport processes.
https://physiology.med.cornell.edu/people/lawrence-palmer-ph-d/
Nikola Pavletich
Our research group is interested in the structural biology of pathways that are altered in cancer, with particular emphasis on pathways that control the growth and proliferation of the cell. In cancer, mutations and other alterations in these pathways lead to the uncoupling of cell growth from growth-regulatory signals and contribute to the unrestricted proliferation of the tumor cell.
https://www.mskcc.org/research/ski/labs/nikola-pavletich
Alexandros Pertsinidis
Our mission is to develop a “new” generation of optical imaging technologies. We aim to analyze macromolecular interactions and motions at the nanometer scale in vivo and to study the three-dimensional architecture of complex molecular machines and subcellular ultrastructures in situ. We also refine and apply ultrahigh-resolution spectroscopy techniques to dissect multistep complex biochemical processes using in vitro reconstituted single-molecule assays.
https://www.mskcc.org/research/ski/labs/alexandros-pertsinidis
Geoffrey Pitt
Our lab focuses on diseases caused by abnormal function of ion channels, specialized proteins in cells that control electrical activity. The lab applies electrophysiology, biochemistry, structural biology, and animal models of human diseases to discern how aberrant ion channel function leads to diseases such as cardiac arrhythmias, neuropsychiatric disorders, ataxias, and epilepsy. Recent work has elucidated novel roles for voltage-gated ion channels in non-excitable tissue and during embryonic development.
https://pittlab.weill.cornell.edu/
Dirk Remus
We are interested in the mechanism of chromosome replication, a process that is highly conserved across eukaryotes and that involves the duplication of both the chromosomal DNA and its associated chromatin states. As chromosomes are the carriers of both the genetic and epigenetic information, faithful chromosome replication is of fundamental importance for genome maintenance during normal cell proliferation. Conversely, defects in chromosome replication are a major driver of the genomic instability observed in cancer cells. To understand the molecular mechanisms by which eukaryotic cells carry out and monitor accurate genome replication we employ a fully reconstituted DNA replication system based on purified proteins from the budding yeast, S. cerevisiae. Research projects are focused on the mechanistic characterization of the core DNA replication machinery, replication-coupled chromatin assembly, DNA replication stress, and S phase checkpoints.
https://www.mskcc.org/research/ski/labs/dirk-remus
Radda Rusinova
My current studies are focused on the role of the lipid bilayer in drug-induced regulation of membrane proteins and teasing apart this general mechanism from direct drug binding. To answer these questions I developed a fluorescence-based stopped-flow assay to monitor changes in the function of KcsA, a prototypical prokaryotic potassium channel, in various well defined lipid environments. These studies will elucidate the role of cell membrane in the membrane protein regulation by lipophilic drugs and thereby provide insight into the mechanism/s underlying multi- and off-target effects of lipophilic drugs.
https://physiology.med.cornell.edu/people/radda-rusinova-ph-d/
Timothy Ryan
The focus of Ryan's lab is on the molecular basis of synaptic transmission in the mammalian brain. We want to understand the regulation of vesicle traffic in presynaptic terminals and how it impacts function and dysfunction. We use biophysical tools to characterize the molecular machinery in living synapses. We use many types of optical assays in combination with molecular, genetic, and chemical tools. In recent years we have also been addressing how endocytosis is regulated at nerve terminals and how vesicles are clustered and mobilized for secretion upon action potential firing.
https://sites.google.com/site/ryanlab1/Home
Simon Scheuring
We perform atomic force microscopy (AFM)-based research of biological samples, with a particular interest in membrane phenomena. Our data reports about the structure, dynamics, diffusion, interaction, mechanics and supramolecular assembly of membrane proteins (channels, transporter and membrane trafficking proteins) and other membrane constituents. The Scheuring Lab offers a truly interdisciplinary environment, where students and postdocs work in fields ranging from membrane protein expression and purification to technical developments making AFM faster and more sensitive.
Stewart Shuman
The goal of my research is to understand the mechanisms and structures of enzymes that perform and regulate essential nucleic acid transactions. My research integrates diverse experimental approaches (including virology, biochemistry, structural biology, and genetics) and applies them to model systems ranging from viruses to bacteria to fungi to mammalian cells. An explicit aim is to identify novel enzymatic targets for treatment of human diseases.
https://www.mskcc.org/research/ski/labs/stewart-shuman
Harel Weinstein
We study mechanisms of membrane-associated macromolecular machines (MAMMs) in cell physiology with methods of molecular and computational biophysics, bioinformatics, and mathematical modeling. New methodological developments for performance and analysis of large-scale computational molecular dynamics simulations are used to learn the underlying structural and dynamic mechanisms of the molecular systems involved in neurotransmission, drug abuse mechanisms, cancer, and currently the Covid-19 virus. In synergistic collaborative studies with experimental labs, we investigate functional mechanisms, allostery, membrane involvement and the design of function-modifying ligands for the MAMMs, including GPCRs, transporters, and TMEM16 membrane lipid scramblases, as well as processes of viral infectivity.
https://physiology.med.cornell.edu/people/harel-weinstein-d-sc/
Xiaolan Zhao
Our lab investigates 3R mechanisms, 3R protein functions and structures, and their links to human disease. Our main research interests include:
- Mechanisms of genome duplication during growth and under stress conditions that mimics carcinogenic exposure or chemotherapeutic treatment.
- DNA repair processes that restore genetic information perturbed by a variety of DNA lesions arising from genotoxic exposures.
- The DNA damage response systems that monitor genome lesion burdens and deploy signaling pathways to induce multi-faceted physiological changes, ranging from metabolic and epigenetic changes, cell cycle delays, to chromosomal organization and maintenance adjustments.
https://www.mskcc.org/research/ski/labs/xiaolan-zhao/overview
Our Trainees
Current Trainees
Past Trainees
Alvarenga, Omar
07/01/2020-06/30/2021
Belay, Viktor
07/01/2021-06/30/2023
Castaneda, Juan
07/01/2021-06/30/2023
Ghani, Vishnu
07/01/2021-06/30/2022
Romano, Giovanna
07/01/2020-06/30/2022