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

Research

My research is focused on understanding the relationship between prolonged exposure to electron micrographs and hallucinations in underpaid, overworked, overcaffeinated, unappreciated, overqualified, abused (by the undergrads), postdoctoral researchers. Everyone accuses me of dilly dallying but I actually come here at 2AM and stare at particles. If you stare long enough at particles, the particle stare back. I also have a dog (son) named Cooper who I actually like staring at. Jenitha is mean to me :( 

Hobbies

Taylor Swift.

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 is the precursor enzyme in polyamine synthesis pathway, it synthesizes putrescine which is essential in biological processes like cell proliferation, regulation of cell death, protein synthesis and cell differentiation. The compelling factor of studying this enzyme lies in its clinical relevance in the progression of Non-small-cell lung cancer. Ornithine decarboxylase is overexpressed with the protein pirin whose elevated levels fosters autophagy inhibition giving cancer cells an avenue to progress rapidly without degradation. This enzyme is also identified as a drug target for treatment of African sleeping sickness disease caused by Trypanosomatids transmitted by tsetse flies. Elevated levels of Ornithine decarboxylase have also been reported in cases of colon cancer. My research focuses on the structural study of the dynamics of Ornithine Decarboxylase to better understand its catalytic action and derive data sets for small molecule virtual screening of inhibitors for drug development purposes. Research steps basically comprise the expression, purification, and crystallization of mouse Ornithine Decarboxylase, including new free-interface diffusion conditions for serial crystallography experiments. Crystals demonstrate the ability to take up substrate and inhibitors, including difluoro methyl-ornithine. Time-resolved and multi-temperature crystallography experiments will probe the reaction mechanism and conformational dynamics, respectively. Molecular dynamics simulations are performed to ascertain the flexibility of the protein computationally and compared with results from multi-temperature crystallography. 

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 The Idiot.

Research

My research involves top-secret information that I don't have the clearance to disclose. Hence, you'll never hear me talk about it. 

Hobbies

Famous choir soloist. I don't have my picture up so that my paparazzi don't find me.

Research

I am responsible for rigorously interrogating the patience level of hired postdocs. Current results have suggested patience is dependent on the level of caffeine in said postdoc. My work has uncovered an inverse relationship between number of questions I ask said postdoc and the level of joy in their life. Also, the HPLC upstairs may one day be violently dismantled and I am telling you now, I had nothing to do with it (I promise).

Hobbies

Running the Chemistry and Biochemistry department.

Bio

I'm studying for the MCAT. I'm probably the only one who is going to have a stable career after this.

Hobbies

Horse girl.

Research

I am here more often than the graduate students. I live here. 

Hobbies

I've been recruited into a Ponzi scheme of TAs and learning assistants. I don't know who to tell.

Research

Dealing with this lab has prematurely made me old and wise. I'm not the same person I was.

Hobbies

Philosophy. Baking.

Research

I study whether extended use of a broken HPLC is damaging to the psychological state of undergraduates.

Hobbies

John Williams.

Research

My research is focused on whether Jenitha is a good mentor. This involves asking her questions 24/7, trying to swallow dangerous chemicals in her presence, and only doing what she asks after the 37th time. Current results suggest her mentees would receive paltry attention and would die in approximately 56.23 seconds after using hazardous lab items. 

Hobbies

Advocating for human rights.