Enhanced Sampling Simulations of Wild Type Epidermal Growth Factor Receptor (EGFR) Oligomers for Future Theraputic Strategies

Principal Investigator: Marat Talipov, Ph.D.

Affiliation/Dept: New Mexico State University, Department of Chemistry & Biochemistry

Description: The Epidermal Growth Factor Receptor (EGFR) is a critical player in cell signaling and is
pivotal for the development and progression of various cancers, including those induced by
radiation exposure, such as in space environments. Recent studies of the EGFR have challenged
its once-assumed role as a prototypical receptor tyrosine kinase, revealing that it employs unique
mechanisms to intricately modulate extracellular signal transduction through a variety of ligation
and oligomerization states. While techniques such as X-ray crystallography, Cryo-EM, and
molecular dynamics have significantly advanced our understanding of EGFR’s structural
aspects, the mechanism of its signal transduction remains a mystery.
In this proposal, we will employ all-atom and coarse-grained molecular dynamics simulations in
conjunction with enhanced sampling techniques to dissect the intricate dynamics of the wild type
monomer and oligomer forms of EGFR. This approach is designed to provide a deeper
understanding of EGFR's functional mechanisms, particularly in the context of cancer
development influenced by radiation exposure. The insights gained from this study will provide a
foundation for future therapeutic strategies, particularly in designing drugs that target and
inactivate constitutively active EGFR mutants while not affecting the wild-type EGFR. This
work will contribute to the field of cancer therapeutics, and it has potential implications for
human health during space exploration, where radiation exposure poses a significant risk.

Novel SiC Structures for Space Exploration

Principal Investigator: Sakineh Chabi

Affiliation/Dept: University of New Mexico, Department of Mechanical Engineering

Description: This project aims to develop a new class of silicon carbide (SiC) materials that can be useful for several space-related applications. As a wide bandgap semiconducting ceramic material with high thermal capability, high voltage breakdown, excellent chemical stability, and strong mechanical properties, SiC is a leading material for high-temperature and high-power applications. For example, while silicon electronics fail at temperatures above 200 °C, silicon carbide components are ideal candidates for high temperatures and extreme environments such as the surface of Venus. Despite several advantages that silicon carbide has over silicon, current SiC technologies are from ideal. Problems include materials quality, rapid oxidation, and poor performance/reliability. To address these problems, we propose to develop a new form of silicon carbide, called 2D SiC, which is expected to be superior to existing SiC materials. The proposed work is innovative and motivated by our recent success in creating the first two-dimensional silicon carbide (2D SiC). Research objectives include (i) fabrication and structural characterization of 2D SiC and related materials, (ii) thermal measurements of the grown materials, and (iii) electrical measurements of SiC nanosheet. The proposed work is directly related to space applications. It aligns with NASA's interest in high-temperature materials/electronics, as well as ultralightweight materials. Thus, receiving this seed funding will enable us to conduct high-impact research to solve scientific and technical problems of importance to NASA. It will also contribute to future research and innovative activities in New Mexico.

Precision Timing of Particles Tracked in Space Investigation of Competing Low Grain Avalanche Detector Technologies

Principal Investigator: Sally Seidel, Ph.D.

Affiliation/Dept: University of New Mexico, Department of Physics and Astronomy

Description: We propose to measure the timing resolution of Low Grain Avalanche Detectors (LGADs) as a function of proton and gamma fluence, for the DC-LGAD, AC-LGAD, and DJ-LGAD technology options, all of which are relevant to devices that could be deployed for space science. This project is consistent with the objectives of the NASA HEOMD, SMD, and STMD directorates. It follows from a prior effort supported by the NMSGC that led to a publication on LGAD gamma ray tolerance, conference presentations, and multiple student research experiences. This works involves the efforts of two New Mexico students and two New Mexico senior researchers and uses irradiation facilities at the Los Alamos National Laboratory and Sandia National Laboratories.