biophysics of dynein motor proteins

Cytoskeletal motor proteins, including the kinesin, myosin and dynein superfamilies, are mechanoenzymes that convert chemical energy to mechanical work. They exert pN-scale forces over nm-scale distances. We focus on dynein, the largest and least studied superfamily. Members of the dynein superfamily are important for cell motility, intracellular transport, mitosis, etc.

Our research is focused on discovering the fundamental physical mechanisms that underlie the action, regulation and coordination of both axonemal and cytoplasmic dyneins. We take multiple approaches including:

  1. optical tweezers
  2. fluorescence and TIRF microscopy
  3. in vitro biological reconstitutions
  4. forward engineered biophysical systems
  5. multiscale mathematical and computational modeling

Most of our fundamental biophysics of axonemal dynein work is done using Chlamydomonas reinhardtii as a model organism.

The tracked flagellar waveforms of the Chlamydomonas beat (Geyer et al. 2013).

Check out our most recent work on this topic on our publications page.

Studying unique biophysical mechanisms of pathogenic parasites

Parasites must adapt to unique, harsh environments that often change as the organism goes through its life cycle. This has resulted in a variety of unique biochemical and biophysical adaptations. The uniqueness of these mechanisms provide promising theraputic targets. In fact, mush of parasitology is focused on understanding and exploiting these mechanisms, typically with techniques from biochemistry, cell biology, molecular biology, genetics and biochemistry.

In the Alper lab, we focus on addressing problems in parasitology through the lens of biophysics and with our collaborators in the Clemson University Eukaryotic Pathogens Innovation Center (EPIC). The application of biophysics to pathogenic parasites. Some of the questions we are working on include:

  1. mechanisms of the "backward" flagellar motion of kinetoplastids
  2. biophysical mechanisms of immune system avoidance in trypanosomes
  3. unique roles of septins in cryptoccus

Trypanosome cells with flagellum attached to cell body (left) and induced to separate from the cell body (right) (Oristian 2017).

Engineering motile biological microstructures

Motile microstructures have been used in engineering applications including for drug delivery, biomedicine and lab on a chip devices. However, traditionally used engineering materials and methods are often inefficient or functionally inadequate for applications at the cellular (10s of micrometers) scale. Engineers have turned to biology for both components from which to build microstructures as well as inspiration for biomimetic solutions.

In the Alper lab, we are expanding the available tools to build and model motile microstructures engineered from cytoskeletal elements.

Entirely biological isolated structures constructed from fluorescently tagged microtubules (shown in white) and axonemal dynein purified from Chlamydomonas flagella (Andorfer 2016).