Amgen Scholars: Announcements of Opportunity

Below are Announcements of Opportunity posted by Caltech faculty for the Amgen Scholars program.

Announcements of Opportunity are posted as they are received. Please check back regularly for new AO submissions! Remember: This is just one way that you can go about identifying a suitable project and/or mentor. For additional tips on identifying a mentor click here.

Please remember:

Students pursuing Amgen must be U.S. citizens, U.S. permanent residents, or students with DACA status.
Students pursuing Amgen must complete the 10-week program from June 21 - August 25, 2023. Students must commit to these dates. No exceptions will be made.
Accepted students must live in provided Caltech housing.

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Project:

Engineering genetically-encoded nanoparticles for efficient protein delivery in plants

Disciplines:

Chemical Engineering, Gene editing, Nanotechnology

Mentor:

Gözde Demirer, Assistant Professor, (CCE), gdemirer@caltech.edu

Mentor URL:

https://www.demirerlab.com/ (opens in new window)

Background:

In a world with a rapidly expanding population, the need for more nutritious, sustainable, and climate-tolerant
plants has become indisputable to mitigate food insecurity. By 2050, the global food demand is
expected to increase by 56%, leading to a 13-fold increase hunger risk. Furthermore, climate change
exacerbates food insecurity by decreasing crop yields by 7.4% for every degree-Celsius change in global
temperature. Traditional breeding has produced crop varieties with improved yield, but it is limited in
utility, scope, and throughput due to its passive role in plant genome engineering. Molecular engineering
and plant biotechnology offer a route to obtaining previously inaccessible crop tolerances.

CRISPR/Cas technology has made targeted and transgene-free genome editing possible in certain plants,
yet there remain critical limitations for ubiquitous application of this powerful system to the wide range of
crops in global demand. A persistent challenge is the delivery of functional biomolecules across the mostly
impervious plant cell wall, which presents a transport problem for intracellular delivery that does not
exist for mammalian cells which can undergo facile transfection. On the other hand, plant genetic
engineering has relied on Agrobacterium (a pathogenic soil microbe) and biolistics to deliver genetic
material across the plant cell wall. However, these methods are limited in cargo diversity, suffer from plant
species-dependence, and cause random transgene insertion. Additionally, they do not allow efficient and
innocuous delivery of functional proteins into plant cells. Considering the desire to avoid transgene
integration in engineered crops, DNA-free gene editing would greatly benefit from the ability to deliver
functional CRISPR/Cas ribonucleoproteins (RNPs) without the need of a plasmid DNA intermediate.

Nanoparticles offer an attractive alternative to traditional biomolecule delivery systems given their ability
to penetrate biological barriers, tunable surface properties, and capability to co-deliver cargoes at greater
capacities, all of which make them effective in mammalian systems. More recently, we have pioneered the
implementation of carbon nanotubes (CNTs) as intracellular delivery vehicles of functional genetic material
into plant cells. While these nanoparticles are remarkable for genetic engineering research, their nondegradable nature and potential environmental toxicity severely hamper field applications. As such, plant genetic engineering needs a biocompatible alternative to CNTs for ubiquitous plant biomolecule delivery.

Our lab draws inspiration from the innate ability of plant viruses, such as tobacco mosaic virus(TMV), to survive long periods of time in the environment and to disassemble and degrade upon cell entry, to design an entirely protein based nanoparticle delivery platform for use in plant genetic engineering. These viruses have
been leveraged for therapeutic cargo delivery in mammalian systems5, but their application for functional protein cargoes and plant cell delivery is entirely untapped.

We hypothesize that TMV plant virus-like particles (pVLPs) can effectively load and deliver functional protein cargoes into plants for DNA-free genome editing. Additionally, owing to the genetic encoding of these self assembled protein nanostructures, we will leverage protein engineering strategies to fine-tune TMV pVLP surface chemistry for a diverse range of applications.

Description:

Aim 1: Develop a pVLP mutant library amenable to bioorthogonal chemistry at engineered stoichiometries.
Aim 2: Characterize pVLP internalization efficiency into plant cells.
Aim 3: Deliver Cas9 RNPs into plants for DNA-free gene editing.

Student Requirements:

Background in molecular and cell biology, gene editing, nanomaterials, or plants will be preferred but not required.

Programs:

This AO can be done under the following programs:

		Program	Available To
		Amgen Scholars	Non-Caltech students only
		SURF	Caltech students only

Click on a program name for program info and application requirements.

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