I studied the kinetic properties of the human mitochondrial ADP/ATP carrier using proteoliposomes and advanced transport robotics
My findings reveal that the transporter operates via a ping-pong kinetic mechanism, where substrate exchange occurs consecutively rather than simultaneously (Cimadamore-Werthein et al., EMBO reports 2023)
Additional collaborative projects have been successfully completed and published (Cimadamore-Werthein et al., EMBO 2024)
Joint PhD in Biochemistry
GlaxoSmithKline
01.2018 - 01.2022
Company Overview: Investigative Preclinical Toxicity Department - Jon Lyon, Director
I investigated the molecular mechanisms of medication-induced mitochondrial dysfunction, focusing on mitochondrial transport proteins as off-targets
By overcoming technical challenges in the characterization of these complex membrane proteins, I identified strong inhibitors of mitochondrial substrate transport, enhancing our understanding of adverse drug effects, gaining new insights into the chemical compound features important for inhibition and informing future therapeutic strategies
This project has been an industrial collaboration with GlaxoSmithKline (UK)
I successfully overexpressed and purified by affinity chromatography, for the first time, the functional and stable human mitochondrial ADP/ATP carrier (AAC) and the human Citrate carrier (CIC) in S
Cerevisiae (mg amounts) (Jaiquel Baron et al., Theranostics 2021)
I developed model systems to assess drug-transporter interactions in high-throughput through thermostability assays and directly measured AAC and CIC inhibition using proteoliposomes and transport robotics
I screened a GSK mitotoxic compound library and the gout medication Benzbromarone was shown to inhibit AAC and CIC with an IC50 of 8.4 μM and 12.5 μM respectively
I discovered that the medication for Parkinson's disease Tolcapone inhibits CIC with an IC50 of 5 μM, three times more potent than its canonical inhibitor benzene tricarboxylic acid
Investigative Preclinical Toxicity Department - Jon Lyon, Director
Research Assistant
MRC Clinical Science Centre, Imperial College London
01.2017 - 12.2017
Company Overview: Laboratory of Redox Metabolism - Dr
Helena Cochemé
I continued working on my master's research project
Laboratory of Redox Metabolism - Dr
Helena Cochemé
Master's Research Project
MRC Clinical Science Centre, Imperial College London
01.2015 - 01.2016
Company Overview: Laboratory of Redox Metabolism - Dr
Helena Cochemé
I discovered that the residual larval fat body in newly eclosed adult Drosophila melanogaster enhances oxidative stress resistance
By genetically and pharmacologically modulating this tissue, I demonstrated that its persistence can either diminish or amplify this resistance
I identified a key regulator of fat body persistence, linking it to lifespan extension
Additionally, I started an RNAi screen to explore the underlying mechanisms, with promising preliminary findings
Laboratory of Redox Metabolism - Dr
Helena Cochemé
Education
MSc - Molecular Medicine
Imperial College London
01.2015 - 01.2016
BSc (Hons) - Genetics
Queen Mary University of London
01.2012 - 01.2015
PhD - Biochemistry
University of Cambridge
01.2018 - 01.2022
Skills
Heterologous Expression of Functional Membrane Proteins in S cerevisiae
Protein Purification - Column and Affinity Chromatography
ELISA
SDS-PAGE
Western-blotting
Bacterial and yeast transformation
Molecular biology
isolation and analysis of bacterial and yeast DNA
Cloning
PCR
RT-PCR
Radioactive uptake assays
Fluorescence and Confocal Microscopy
Cell Culture
Seahorse XF
NanoDFS
Protein Crystallography
Drosophila husbandry
UAS/GAL4 system
RNAi lines
dissection
Bioinformatics
BLAST
ClustalW
PyMOL
use of R
GraphPad Prism
MS Office Suite
Nationalities
British
Colombian
Personal Information
Work Permit: Canadian work permit
Research
Postdoctoral Research Associate, Mitochondrial Biology Unit, Cambridge University, UK, 08/01/22, 07/31/23, Prof. Dr. Edmund Kunji, Studied the kinetic properties of the human mitochondrial ADP/ATP carrier using proteoliposomes and advanced transport robotics.
Joint PhD in Biochemistry, Laboratory of Mitochondrial Transport Proteins, GlaxoSmithKline, Stevenage, UK, 08/01/18, 07/31/22, Prof. Dr. Edmund Kunji / Jon Lyon, Investigated the molecular mechanisms of medication-induced mitochondrial dysfunction.
Research Assistant, MRC Clinical Science Centre, Imperial College London, UK, 01/01/17, 12/31/17, Dr. Helena Cochemé, Continued working on master's research project.
Master's Research Project, MRC Clinical Science Centre, Imperial College London, UK, 09/01/15, 08/31/16, Dr. Helena Cochemé, Discovered that the residual larval fat body in newly eclosed adult Drosophila melanogaster enhances oxidative stress resistance.
Publications
Mitochondrial carriers function as monomers exchanging substrates with a ping-pong kinetic mechanism, Cimadamore-Werthein C, King MS, Lacabanne D, Pyrihová E, Jaiquel Baron S, Kunji ER, The EMBO Journal, 2024, 10.1038/s44318-024-00150-0
Human mitochondrial ADP/ATP carrier SLC25A4 operates with a ping-pong kinetic mechanism, Cimadamore-Werthein C
Jaiquel Baron S
King MS, Springett R, Kunji ER, EMBO Reports, 08/03/2023, 10.15252/embr.202357127
Characterization of drug-induced human mitochondrial ADP/ATP carrier inhibition, Jaiquel Baron S, King MS, Kunji ERS, Schirris TJJ, Theranostics, 2021, 11, 11, 5077-5091, 10.7150/thno.54936
Scholarshipsandawards
2018, Awarded the Biotechnology and Biological Sciences Research Council (BBSRC) Industrial Collaborative studentship to fund my PhD in partnership with GSK
2016, Awarded the highest grade (90%) of the MSc course for my research project (Imperial College London, 1ST Class Hons)
2012, Awarded the 'International Science and Engineering Undergraduate Excellence Award' (£5,000) for being the highest-achieving overseas applicant (Queen Mary University of London)
Training
2022, MBU annual symposium, poster
2019, International BMT Conference, poster
2018, The London fly meeting - The Francis Crick Institute, London, talk
Timeline
Postdoctoral Research Associate
Mitochondrial Biology Unit, Cambridge University
01.2022 - 01.2023
Joint PhD in Biochemistry
GlaxoSmithKline
01.2018 - 01.2022
PhD - Biochemistry
University of Cambridge
01.2018 - 01.2022
Research Assistant
MRC Clinical Science Centre, Imperial College London
01.2017 - 12.2017
Master's Research Project
MRC Clinical Science Centre, Imperial College London
Graduate Research Assistant at Cell Biology and Genetics Unit, University of IbadanGraduate Research Assistant at Cell Biology and Genetics Unit, University of Ibadan