FIRST AND LAST NAME, MD, PHD

ORIGINAL RESEARCH CONTRIBUTIONS SUMMARY

Field of Expertise:
Biophysics, with specialization in Bottom-up reconstitution of cellular processes

Original research accomplishment #1

Project Title: Insights into phagosome maturation using magnetic tweezers

This was the work carried out during Dr. (Last Name)’s Ph.D. studies.

Project Description: Phagocytosis is the process by which immune cells of our body eliminate
pathogens that would otherwise cause disease. This process involves internalization of pathogens
by phagocytic cells in an organelle called as phagosome. Upon internalization, phagosome is
transported from the periphery of the immune cell towards the nucleus in a centripetal fashion.
This transport has long been considered as a pre-requisite for the cell to be able to “mature” the
phagosome by its acidification which leads to degradation and elimination of the pathogen inside
the phagosome.

Project Objective: Although a relationship between a phagosome’s centripetal transport and

pathogen degradation has long been expected, a direct causal link had yet to be established.
Earlier studies established this relationship by showing that disruption of the cellular transport
tracks “cytoskeleton” prevents phagosome degradation. However, cellular cytoskeleton is
important for a number of other processes and preventing its normal assembly would be expected
to disturb a number of key processes. Therefore, Dr. (Last Name) and colleagues decided to
physically hinder the transport of the phagosome using magnetic tweezers. Cells were allowed to
phagocytose pathogen mimicking magnetic particles. Magnetic force was then applied on these
particles to prevent their motion. Further, phagosomal acidification and maturation was
measured using pH-dye attached on the magnetic particle.

Key outcome of the project: Dr. (Last Name) and colleagues showed that preventing
phagosomal motion leads to delay in acidification of the phagosome and subsequent degradation
of the pathogen.

Significance/Originality of Dr. (Last Name)’s Collaborative Work: A number of pathogens,

like the bacteria responsible for tuberculosis, delay phagosomal acidification; however, not much
is known what mechanisms pathogens exploit to do this. Dr. (Last Name) and colleagues showed
that preventing a phagosome’s motion is one such mechanism. They further showed that the
mechanical environment of the phagosome remains unchanged as the phagosome matures.

Please discuss whether it has been implemented yet in the field, whether academically or in
industry practice. Dr. (Last Name) published two primary author papers in Biophysical Journal
and Sensors and Actuators B: Chemical on this work, and this technique was highlighted as an

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“Emerging Biophysical Technology” in 2012 by the Biophysical Journal. Dr. (Last Name) and
colleagues were also invited to write a detailed methods paper in the journal Methods in
Molecular Biology on this topic so others could implement it.

Original research accomplishment #2

Project Title: Regulation of the actin filament growth by competition between molecular
machineries

Project Description: This work included two sub-projects. 1) The dynamic nature of the actin
cytoskeleton lies at the heart of a number of cellular processes, like cell movement, cell division,
wound healing, etc. Formins are known to bind the plus ends of actin filaments and accelerate
their elongation. Capping proteins are known to bind growing ends of actin filaments and
prevent their elongation. For the last few decades, capping protein and formin were thought to
bind the filament ends in a mutually exclusive manner (i.e., only one of them could bind at a
time). This presented a conundrum: how do cells stop formin-elongating filaments from growing
uncontrolled? Dr. (Last Name) and colleagues demonstrated that in contrast to existing view,
formin and capping protein can simultaneously bind barbed ends to form a multicomponent
“decision complex”. As a result of this, both capping protein and formin catalyze each other’s
displacement. 2) In the second project, Dr. (Last Name) and colleagues demonstrated that
profilin, a ubiquitous actin monomer binding protein, controls the balance between linear and
branched actin networks and competes with formin and capping protein for barbed-end binding.

Key outcome of the project: These unique mechanisms provided us with unprecedented
understanding of how multiple protein regulators compete and collaborate to exert fine control
on size of actin containing cellular organelles such as filopodia.

Significance/Originality of Dr. (Last Name)’s Collaborative Work: This work led to two

major publications in Developmental Cell and Nature Communications.

Original research accomplishment #3

Project Title: Depolymerization of the actin cytoskeleton

Project Description: This work includes two sub-projects. 1) The rate limiting step in a cell’s
ability to use actin polymerization for its motility is depolymerization of pre-existing actin
networks to generate monomers required for polymerization of new filaments. Dr. (Last Name)
and colleagues discovered the first direct evidence of actin filament depolymerization by
ADF/Cofilin protein family, which has long been predicted and debated. Their experiments
demonstrated its dual function on actin filaments – filament severing and enhanced
depolymerization. 2) Dr. (Last Name) and colleagues also discovered a novel multicomponent
pathway of actin filament depolymerization in which cyclase-associated protein (Srv2/CAP)
synergizes with cofilin to enhance pointed-end depolymerization of an actin filament by ~ 350-
fold (54 s-1); these are the fastest rates of actin turnover ever observed in vitro.

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Key outcome: These are the first direct demonstration of how living cells can depolymerize their
actin cytoskeleton.

Significance/Originality of Dr. (Last Name)’s Collaborative Work: These two studies led to a

publication in the journal Current Biology and a second manuscript that is currently under review
at Nature Communications. Both of these studies were possible due to a novel of a microfluidics-
assisted Total internal reflection microscopy (TIRF) approach. Dr. (Last Name) has since
established this methodology in the labs of his mentors in Boston. Only two labs in the world
have this microfluidics-assisted TIRF approach to study single filament actin dynamics. Dr. (Last
Name)’s lab in Boston is the only one in the United States. Moreover, Dr. (Last Name) has been
invited to write a single author methods paper for this technique in the journal Current Protocols
in Cell Biology.

Original research accomplishment #4

Name/Title of Project: Development of Stentor coeruleus as a model system to study the

evolution of multicellularity

Description: How did multicellular organisms evolve? This has been one of the most intriguing,
yet unsolved questions facing biologists studying evolution. The first multicellular organisms
arguably evolved by many unicellular organisms aggregating together for common benefit. In
collaboration with Professor (Name) at the University of California San Francisto, Dr. (Last
Name) is developing Stentor coeruleus as a model organism to study the evolution of
multicellularity. Stentors can live both as solitary organisms and can also form colonies
containing a large number of individuals. Dr. (Last Name)’s goal was to determine the benefits
Stentors gain by forming colonies.

Key outcome of the project: Dr. (Last Name) showed that when individuals come together,
their feeding flows (mechanism to feed themselves) get hydrodynamically coupled and they can
feed better, thus demonstrating a direct benefit of multicellular-like behavior.

Significance/Originality of Dr. (Last Name)’s Work: Dr. (Last Name) completely and

independently established this project addressing a fundamentally important evolutionary
question. He has twice been awarded the Whitman Early Career Award to carry out
independent summer research at the Marine Biological Laboratory at Woods Hole,
Massachusetts. He has also been awarded Provost Innovator Inquiry Award and research
grant for this work. A manuscript on this work is currently under submission.

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