Research

In my lab we study the structure and dynamics of proteins so we can better understand how proteins perform the physical and chemical jobs they do in the living cell. Of particular interest to us are enzymes, which are proteins that catalyze chemical reactions. Enzymes are quite amazing catalysts that biology has developed to carry out often challenging organic chemistry while being limited to primarily carbon, nitrogen, oxygen, and hydrogen, as well as a handful of cofactors. Enzymes accomplish this task due to their three-dimensional structure.

However, knowing a structure of an enzyme is often not enough to fully appreciate the catalytic mechanism (that is, how the enzyme accomplishes the chemistry) of these proteins, as their structure changes when interacting with the environment, binding substrates, and catalyzing the reaction. Therefore, my lab specializes in time-resolved methods where we capture intermediate structural states along a reaction path while it is in progress. That allows us to watch the chemistry in action and understand how the protein moves while it is performing reactions. These challenging experiments require millisecond time resolution and much of my career has been devoted to developing new techniques to observe these reactions more easily.

Education

Postdoctoral Researcher, Laboratory of Atomic and Solid-State Physics
Cornell University, 2019-2022

Postdoctoral Fellow, Department of Biosciences
Rice University, 2018-2019

PhD. Biochemistry
Rice University, 2012-2018

B.S. Biochemistry
Lipscomb University, 2008-2012

Experience

Assistant Professor
Baylor University 2022-present

Education

Postdoctoral Fellow, Department of Chemistry and Biochemistry
Baylor University, 2024-Present

PhD. Biochemistry
Baylor University, 2018-2024

B.S. Chemistry
Siena College, 2014-2018

Research

Ornithine Decarboxylase 

Ornithine decarboxylase (ODC) is a pyridoxal-5′-phosphate (PLP) dependent enzyme that catalyzes the decarboxylation of L-ornithine to putrescine, a critical step in polyamine biosynthesis. Polyamines such as putrescine, spermidine, and spermine are essential for cell proliferation, differentiation, and gene regulation. Dysregulated ODC activity has been implicated in cancer, and parasitic diseases, making it a target for therapeutic intervention. As of today, the only FDA approved inhibitor for ODC is difluoromethyl ornithine, a substrate mimic, approved only in African sleeping sickness caused by the protozoan parasite of the specie Trypanosoma brucei but there is no current FDA approved inhibitor of ODC for treatment of cancer and neurological disorders. My research is focused on investigating the structural dynamics and catalytic mechanism of ODC through time-resolved x-ray crystallography and multi-temperature x-ray crystallography to obtain structural datasets that aid in a better understanding of the enzyme catalysis and can be used for downstream structure-based drug design of ODC inhibitors.

Urease

Urease is a nickel-dependent metalloenzyme that catalyzes the hydrolysis of urea into ammonia and carbon dioxide at a rate enhancement of ~10^14  than the uncatalyzed reaction, underscoring its status as one of the most highly efficient enzymes identified. This reaction plays a critical role in nitrogen metabolism in plants, fungi, and bacteria. In pathogenic bacteria such as Helicobacter pylori, urease activity enables survival in acidic environments by locally increasing pH through ammonia production, contributing to urinary tract infections and gastric cancer, hence there has been a need to develop safe and efficient urease inhibitors. My research is focused on investigation of the chemical and structural events during catalysis by utilizing multi-temperature x-ray crystallography to develop insights that strengthens the mechanistic foundation for developing structure-based urease inhibitors targeting H. pylori infections and reducing nitrogen loss in agriculture.

Education

PhD Student, Biochemistry

Baylor University, 2022-Present

B.Tech, Science Laboratory Technology (Biochemistry major)

Federal University of Technology, Imo State, Nigeria; 2016-2021

Hobbies

Cooking unbearably spicy "spaghetti"; anything with chocolate.

Research

I joined the Clinger lab in the winter of 2022. Since then, I've worked on a variety of projects. My ongoing ones are as follows:

1. Temperature resolved X-ray crystallography of calicheamicin-synthase 11 (CalS11). CalS11 is a little explored protein involved in the synthesis of the anti-cancer antibiotic, calicheamicin. It features disordered L2 and L5 regions, the L2 region of which has been shown to act as a flexible gating loop upon binding with ligand SAM. As such, this flexible protein is of high interest as a model to understand different conformational states occupied by gating loop proteins. I plan to investigate these conformational states by observing them in response to temperature variations implemented at the beamline during synchrotron data collection. 

2. Variable temperature circular dichroism (CD) of laser-ablated proteins. Laser ablation is a common technique used in matrix-assisted laser desorption ionization (MALDI) to ionize proteins. It has remained untested whether the ultrafast ablation process causes minute structural shifts or misfolding in the sample. By using CD to observe secondary structural changes, my research should clarify the interference of laser ablation as a method. Furthermore, melting curves collected using CD will be used to observe whether the Tm of the proteins investigated have changed due to the ablation process, which would be indicative of structural change. My model proteins include the standard model protein BSA, the metal-center protein carbonic anhydrase, and the beta-sheet rich GFP. This project is in collaboration with the Solouki at Baylor University.

3. CryoEM imaging of Drosophila atlastin (ATL). ATL is a membrane fusion protein involved in joining opposing vesicular lipid membranes to one another. Its misfunction has been linked to hereditary spastic paraplegia, which leads to immobility of the lower limbs, and hereditary autonomous neuroplegia, which leads to painless injuries. It is involved in synaptic nerve pathway generation and creation of three-way junctions in the endoplasmic reticulum. Its fusion capabilities are carried out by some unclear movement of the C-terminal tail, which is proposed to be alpha helical. In spite of being highly researched, to date no structure has been published which actually shows its C-terminal tail. I plan to use cryo-EM, circumventing prior challenges with crystallizing a membrane protein, to obtain high-resolution images of full length ATL.

Education

Ph.D. Student, Chemistry
Baylor University, 2022-Present

B.S. Biological Sciences
Southeastern Louisiana University, 2018-2022

Hobbies

Building lab websites.

Research

I joined the Clinger lab in January 2023, and I work on different projects; they are as follows:

Spermine synthase and spermidine synthase

Spermine synthase (SPS) and spermidine synthase (SPDS) are important polyamine biosynthetic enzymes that catalyze the synthesis of polyamines. SPS produces polyamine, spermine, from spermidine, while SPDS produces spermidine from putrescine, both utilizing decarboxylated S-adenosine methionine as the amino propyl donor. These polyamines are important for cell growth and development, and the enzymes are highly implicated in cancer cells, making them an important target for the development of therapeutics. I will be carrying out time-resolved crystallography and multitemperature crystallography on these enzymes to determine their structures at different points during catalysis and also at different temperatures. This will enable us to know the dynamics and important residues for catalysis. Detailed information about the structure of the enzymes will facilitate the design of inhibitors for spermine synthase and spermidine synthase for cancer therapy.

C-prenyltransferase

C-prenyltransferase (PriB) is a natural product biosynthetic enzyme that catalyzes the prenylation of indole compounds. Prenylated natural products, including prenylated indole derivatives, exhibit a wide range of biological activities. I will be studying the loop dynamics of this enzyme, understanding the important residues responsible for the opening and closing of the loop that covers the active site. I will use time-resolved crystallography and multitemperature crystallography to study the energy landscape of PriB.

Education

Ph.D. Chemistry

Baylor University, 2022-Present

M.Tech. Biochemistry

Federal University of Technology Akure, 2019-2021

B.Tech. Biochemistry

Federal University of Technology Akure, 2012-2017

Hobbies

Dancing to great singers, particularly Celine Dion.

Research

Time-resolved and Multitemperature X-ray crystallography of proline dehydrogenase (PRODH) enzyme. During proline catabolism reaction, the overexpression of PRODH enzyme causes the increase production of ATP and reactive oxygen species (ROS) which is responsible for the proliferation of cancer cell and tumor growth. As a result, PRODH enzyme is considered as one of the targets of breast and lung cancer therapeutics. I have plan to interrogate the conformational states of the intermediate structure to better understand the structural transitions and the functional roles of its gating loop, which are crucial for understanding how PRODH overexpression influences cancer progression. In this project, I employ time-resolved and multitemperature X-ray crystallography methods which are incredible techniques to gain insight into the enzyme’s structural transitions.

Education

Ph.D Student, Biochemistry
Baylor University, 2022-Present

MS. Organic Chemistry
University of Chittagong, Bangladesh, 2019-2020

B. Sc. Chemistry
University of Chittagong, Bangladesh, 2015-2018

Background

Born in Chattogram, Bangladesh

Joined the Clinger lab in Spring 2023

Hobbies

Hanging out with my family, travelling with my husband, love to cook food.

Research

My projects are focused on probing the energy landscape of lactate dehydrogenase (LDH) using experimental and computational techniques. Specifically, I am working on:

1. Multi-temperature crystallography of LDH.
   Historically, most diffraction datasets were collected at cryogenic temperatures. This was found to introduce bias into the solved structure and not reflect the structure at physiological temperature. Moreover, manipulation of the data collection temperature allows population of higher energy conformations. This can lend temperature-resolved insights into the energy landscape. My project focuses on performing MTX on LDH to remove the cryogenic bias from current LDH structures, and gain insights into the energy landscape of LDH.

2. Molecular Dynamics Simulations of Protein Crystals
   Molecular dynamics (MD) is quickly becoming a staple in structural biology labs. My work is interested in integrating MD with protein crystallography workflows. Specifically, I am interested in using MD to recapitulate MTX results. MTX experiments, while important, are time-consuming and expensive. For this reason, I am investigating whether the use of MD can obviate the need to perform MTX experiments.

3. Temperature-Jump Crystallography of LDH
   LDH has been proposed to possess a "promoting vibration" (PV) facilitating catalysis. A PV is a network of residues propagating from the active site to the solvent that allows transfer of thermal energy. Computational studies of LDH have suggested the existence of a PV. However, empirical evidence is indirect. I intend to study LDH using temperature-jump (T-Jump) crystallography. T-Jump Crystallography involves irradiating the protein crystal with an IR laser and then measuring the diffraction image at set time points after irradiation. This will allow a time-resolved picture into the thermal relaxation. My project aims to apply this technique to stimulate and detect the PV in LDH.

Education

Ph.D Student, Chemistry
Baylor University, 2023-Present

B.S. Chemistry
New Mexico Tech, 2020-2023

Hobbies

Dumpster diving; inhaling tortillas with honey; procrastinating finishing Don Quixote.

Fair Abbie Ramsey, a scholar in her third year of the noble art of biochemistry, hails from the warm and fertile lands of Louisiana. A triplet by birth, she was reared in the fellowship of shared beginnings, where kinship and tender care first stirred within her the calling to heal. With earnest mind she studies the mysteries of lactate dehydrogenase, tracing the hidden alchemy by which life’s humors are sustained and ailments revealed. Toward the gentle craft of pediatrics her heart inclines, that she might one day minister to the youngest souls with both learned skill and kindly grace.