Research Areas

The Biophysics Graduate Program offers seven areas of research emphasis:

  1. Biophysical approaches to cell biology
  2. Complex biological systems
  3. Computational and theoretical biophysics
  4. Membrane biophysics
  5. Protein engineering and synthetic biology
  6. Proteomics and genomics
  7. Structural biology

1. Biophysical approaches to cell biology

The fields of molecular and cellular biology are exceptionally strong at UCSF, and many faculty members in these areas use cutting-edge tools of biophysics. These approaches include quantitative analyses of chaperones, protein- and RNA-based assemblies, motor proteins, enzymes, receptors, ion channels and transport proteins, protein-ligand complexes, and viral-host complexes. Research in quantitative cell biology also includes studies of chromosomes and centrosomes, proteosomes, clathrin-coated vesicles, synaptic vesicles, actin cytoskeleton, and organelle biogenesis.

The strengths of our program at UCSF encompass:

  • Atom-level analyses using physics-based methods and fundamental principles of physical chemistry.
  • Protein folding in vivo, protein sorting, and macromolecule dynamics.
  • Regulation of transcription and translation.
  • mRNA export, RNA splicing and turnover.
  • Quantitative analyses of gene regulatory networks.
  • Network feedback control by kinases.
  • Spatial and temporal control networks.
  • Mechanisms of chromatin remodeling and transmembrane signaling.
  • Molecular basis of electrical signaling and synaptic plasticity.
  • Engineering and physical principles underlying cellular morphogenesis.
  • Cell fate determination.
  • Cell polarity and migration.
  • Cellular energy metabolism.
  • Apoptosis and cancer.
  • Drug discovery and delivery.

Other innovations such as molecular evolution, microfabrication and nanofabrication, biomimetic architecture design, and programmed assembly of three-dimensional tissues create opportunities to validate our understanding and develop novel therapeutics. What makes our research community unique is the ease of combining expertise to solve biological questions of interest.

Core faculty members:

2. Complex biological systems

The designated emphasis in Complex Biological Systems has brought together a group of investigators with research interests in computational and systems biology. The focus of these laboratories is to understand the overarching organizational principles that underlie the operation of biological networks in health and their failure in disease.

Research areas span systems operating at multiple biological scales, ranging from gene networks to communities of cells and organisms. We emphasize both the reverse-engineering of endogenous biological networks and the forward-engineering of synthetic ones. These investigations pose a number of challenges, which are addressed using strong emphasis on the development of cutting-edge computational and experimental technologies.

Close interactions among the systems biology investigators and the biophysics and bioinformatics research groups provide for a fertile multidisciplinary environment in graduate training. In addition, a seamless interface between the complex biological systems and the vibrant cell, molecular, and developmental biology communities at UCSF catalyzes productive and close-knit iterations between computation and experimentation. These interactions rapidly advance our knowledge of how biological systems achieve their emergent properties.

Core faculty members:

3. Computational and theoretical biophysics

Computational and theoretical biophysics have been strengths at UCSF for decades. Early, influential contributions included the first widely used computer-aided drug design program (DOCK, developed originally by Irwin "Tack" Kuntz and currently led by Brian Shoichet's group) and the AMBER molecular dynamics program developed by the late Peter Kollman.

We continue to have very strong efforts in molecular modeling, which have expanded into areas such as comparative modeling, cheminformatics, and protein design, and we are building new strengths in computational systems biology and multi-scale modeling.

All of our faculty members either have their own wet laboratory experimental efforts or collaborate extensively with others with wet laboratories.

Core faculty members:

4. Membrane biophysics

Membrane Biophysics studies the function and structure of biological membranes, in particular the molecules that endow cell membranes with their extraordinary properties. The UCSF Membrane Biophysics subgroup comprises a group of exceptionally strong laboratories interested in ion channels and membrane transport proteins, membrane receptors and signaling pathways associated with biological membranes, as well as membrane trafficking. The faculty in the group are interested not only in the function of molecules that compose biological membranes, but in how these functions are encoded by structure. Participation in activities of the Membrane Biophysics subgroup will provide students a strong background in both classical and emergent methods of biophysics, biochemistry and structural biology. The questions addressed by these groups also have relevance for diverse fields, from cell biology and neuroscience to fertilization, aging, cardiac and neuropsychiatric disease.

Core faculty members:

5. Protein engineering and synthetic biology

UCSF has a small but exceptionally strong group of faculty members with expertise in protein engineering, using both computational and experimental methods. The tools of protein engineering are being used to advance both human health (therapeutic antibodies, medical imaging) and the goals of synthetic biology.

Core faculty members:

6. Proteomics and genomics

Presently, there is an exponential increase of genome sequence information being derived from a wide variety of organisms using next-generation sequencing technologies. One major next step is trying to elucidate the function of the annotated genes using functional proteomic platforms, which are both experimental and computational in nature. For example, identifying and characterizing the physical connections between different proteins is essential in understanding gene function.

State-of-the-art mass spectrometry is often used to identify protein-protein interactions in a variety of systems and this information is exploited by many scientists at UCSF, including those focused on systems, structural, and computational biology.

Furthermore, global and targeted study of post-translational modifications (PTMs) of proteins is also carried out at UCSF, and these specific PTMs are used to understand the biological and structural connections between different protein-protein interactions.

Ultimately, this information is highly complementary to data obtained from genomic approaches available at UCSF and combined, they are crucial in understanding complex biological phenomenon.

Core faculty members:

7. Structural biology

UCSF has been a pioneer in structural biology for more than three decades. Our historic strengths in X-ray crystallography and nuclear magnetic resonance have now been expanded to efforts in cryoelectron microscopy and high-resolution microscopy. Structural biology at UCSF benefits from a wide range of core facilities, including those in the Macromolecular Structural Group.

Core faculty members: