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Department of

Chemistry

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Monica Rieth headshot

Monica Rieth

Visiting Assistant Professor

mdr205@lehigh.edu
Education:

Ph.D. Chemistry, 2014 (conferred), Lehigh University, Bethlehem, PA

M.S. Pharmaceutical Chemistry, 2007, Lehigh University, Bethlehem, PA

B.S. Biochemistry, 2003, University of Delaware, Newark, DE

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Additional Interests

  • Bioengineering & Synthetic Biology

Research Statement

Background

Lipid aggregates, such as liposomes and micelles, play critical roles in biological systems and have significant applications in drug delivery, membrane biology, and nanotechnology. These aggregates are typically composed of different lipid species, each contributing unique physicochemical properties to the overall structure. Understanding the heterogeneity within these lipid assemblies is crucial, as it can affect their functionality, stability, and interaction with other biomolecules. Despite advances in lipidomics and microscopy, comprehensive methodologies for assessing lipid heterogeneity in lipid aggregates remain underdeveloped. This proposal aims to develop and apply innovative techniques to characterize lipid diversity within aggregates at a high spatial and compositional resolution.

Key Objectives

The main objective of this research is to assess lipid heterogeneity in lipid aggregates, focusing on the following goals:

  1. Characterize lipid composition: Identify and quantify different lipid species within the aggregates.
  2. Analyze spatial distribution: Investigate the localization of different lipid species within the aggregates to understand microdomain formation and lipid clustering.
  3. Correlate lipid composition with function: Examine how lipid heterogeneity influences the physical and biological properties of the aggregates, such as permeability, stability, and interaction with proteins.

Methodology

To assess lipid heterogeneity, the following multi-step approach will be utilized:

  1. Fluorescence Microscopy and Super-Resolution Techniques:
     To visualize the spatial distribution of lipid species, fluorescence microscopy, coupled with super-resolution imaging techniques (such as expansion microscopy, ExM), will be employed. Fluorescently labeled lipid analogs will allow the tracking of lipid species within the aggregates, enabling the identification of lipid domains and phase separation within the structure. These data will further provide high-resolution structural information regarding the organization of lipids in these aggregates, allowing us to correlate lipid heterogeneity with physical properties like aggregate size, curvature and stability.
  2. Functional Analysis (Time permitting):
     To assess the functional implications of lipid heterogeneity, experiments will be designed to evaluate the interaction of lipid aggregates with model proteins and small molecules. Techniques like isothermal titration calorimetry (ITC) or differential scanning calorimetry (DSC) along with dynamic light scattering (DLS) will be used to measure binding affinities, aggregate size, and stability changes as a result of lipid diversity and biomolecular composition.

Conclusion

Assessing lipid heterogeneity in lipid aggregates will advance our understanding of lipid organization and function in biological membranes and synthetic systems. The proposed research will also contribute to the rational design of lipid-based delivery systems by providing insights into how lipid composition impacts aggregate behavior and functionality. By integrating advanced imaging and biophysical methods, this project aims to provide a comprehensive approach to studying lipid heterogeneity and its implications for lipid aggregate performance in various biological and technological applications.

References

  • Wang, S., Shin T.W., Yode, H.B., McMillan R.B., Hanquan S., Liu Y., Zhang C., Leung K.S., Yin P., Kiessling L.L., Boyden E.S. (2024). Single-shot 20-fold expansion microscopy. Nat Methods. https://doi.org/10.1038/s41592-024-02454-9
  • Rieth MD. (2022).  “A new lipid complex has micelle and bicelle-like properties.” BBA – Biomembranes. 1864(9): 183952. https://doi.org/10.1016/j.bbamem.2022.183952
  • Rieth MD, Root K.T., K.J. Glover. (2020). “Reconstitution of full-length caveolin-1 into phospholipid bicelles: validation by analytical ultracentrifugation.” Biophys. Chem. 259: 106339.  https://doi.org/10.1016/j.bpc.2020.106339
  • Rieth MD* & Lozano A.J.  (2020). “Preparation of DPPC liposomes using probe-tip sonication: investigating intrinsic factors affecting temperature phase transitions.”  Biochem. Biophys. Rep. 22: 100764. doi.org/10.1016/j.bbrep.2020.100764
  • Wassie, A.T., Zhao Y. & Boyden E.S. (2019). Expansion microscopy: principles and uses in biological research. Nat Methods 16, 33–41. https://doi.org/10.1038/s41592-018-0219-4

Biography

Monica Rieth began her independent scientific career as an Assistant Professor in the Department of Chemistry at Southern Illinois University in Edwardsville (IL).

Before starting her tenure-track position in 2017 she held a postdoctoral appointment at the University of California, Santa Barbara in the Department of Chemical Engineering investigating the oligomeric behavior of the human adenosine A2a receptor, a G-protein coupled receptor linked to human health and disease. Dr. Rieth obtained her Ph.D. in Biochemistry from Lehigh University under the supervision of Professor Jebrell Glover, a pioneering leader in the field of caveolin structural biology.

Her own research is aimed at investigating protein structure and function using a combination of biophysical and cell biology-based tools to probe their behavior in an effort to better understand the implications of anomalous changes to their sequence. To achieve this, her lab incorporates rational protein design and engineering along with synthetic biology to effectively express and produce these proteins in heterologous organisms. This allows important biochemical and biophysical aspects of protein structure to be interrogated in vitro and in vivo.

To date, her research can be found published in peer-reviewed journals and in posted preprints.

In addition to research, Prof. Rieth has spent considerable time devoted to applying and developing active learning methods in the lab and classroom. The results of these efforts can also be found in published peer-reviewed papers on course development in biophysics as well as developing a research training curriculum geared toward undergraduates in a "research" lab environment (paper in revision).

Dr. Rieth left the Chemistry department at SIU (Edwardsville) in spring 2022 pending a move to Berkeley, CA.

Selected Manuscripts

  • M.D. Rieth. (2025). “Pushing the limits of structure prediction in regions of disorder using ColabFold: Progress and insights.” bioRxiv [Preprint]. Jan. 2, 2025. Available from: https://doi.org/10.1101/2024.12.31.630938.
  • T.N. Ozturk, P. Soto, C. Bores-Quijano, M.D. Rieth, J.R. Koeppe. (2024). “Developing Core Competencies for Undergraduate Instruction in Molecular Biophysics.” BMBEd. In revision.
  • M.D. Rieth. (2023). “Re-examining structural features of caveolin: 25 years later.” Authorea [Preprint – Review article].   June 6, 2023. Available from: https://doi.org/10.22541/au.168607348.84832546/v1. (Journal submission pending)
  • M.D. Rieth. (2022).  “A new lipid complex has micelle and bicelle-like properties.” BBA – Biomembranes. 1864(9): 183952.
  • Rashmi Karki, Swechha Rimal and M.D. Rieth.* (2021). “Predicted N-terminal N-linked glycosylation sites may underlie membrane protein expression in Saccharomyces cerevisiae.” Yeast. 39(9): doi.org/10.1002/yea.3657.

Selected Presentations

  • Rieth MD. “Mapping key residues of a known protein structure using AF2-ColabFold.” Oral talk presented at: NYU AI in Chemistry Summit. 2025 June 25-27; New York, NY, USA
  • Quijano-Bores C, Koeppe JR, Ozturk TN, Rieth MD, Soto P. “Developing Core Competencies for Undergraduate Instruction in Molecular Biophysics.” Oral talk presented by C. Bores-Quijano at: American Physical Society. 2025 March 16-21; Anaheim, CA, USA     
  • Rieth MD. “Spectroscopic properties of an environmental pollutant enable detection and quantitation after liposomal capture.” Division of Analytical Chemistry. Oral (virtual) talk presented at: American Chemical Society. 2023 August 13-17; San Francisco, CA, USA. Hybrid
  • Rieth MD. “Unstructured protein targets for therapeutic intervention.” Division of Biochemical Technology. Poster (live) presented at: American Chemical Society. General Papers. 2023 August 13-17; San Francisco, CA, USA. Hybrid
  • Rieth MD.  “Tailoring naturally sourced lipids and proteins toward the development of novel biomaterials.” Poster presented at: Gordon Research Conference on Bioinspired Materials. 2022 June 5-10; Les Diablerets, Switzerland.
    doi.org/10.13140/RG.2.2.12869.83685

Teaching

Current courses:

Elements of Biochemistry I, CHM/BIOS 371
Lipids and Membranes, CHM 373/472 

Website

Rieth Lab