RepState Doctoral Candidates

Vaishnavi Bahukelar

Erasmus MC, NL
Insight into the role of ATP hydrolysis during DNA mismatch repair initiation through biophysical and functional analysis

Margherita Fini

University of Bristol, UK
Symmetry and Asymmetry in Nucleotide Excision Repair of DNA

Khalid Rasheed

Justus Liebig University, DE
Function of the MutL state machine

Emma Arean-Ulloa

Leiden University Medical Center, NL
Unraveling the organization of the mismatch strand removal process

Pratiksha Mall

Netherlands Cancer Institute, NL
Structure and Function of the MutSα and MutLα state machines

Abigail Jean Russel

University of Bristol, UK
Non-canonical roles for UvrD in DNA repair

Patrick Chirdon

University of Leeds, UK
Structural mass spectrometry for the analysis of nucleic-acid: protein interactions and applications in the study of DNA repair complexes

Devendra Singh

French National Centre for Scientific Research, FR
Single-molecule characterization of transcription-coupled DNA repair

​​Aamna Sajid

French National Centre for Scientific Research, FR
Single-molecule characterization of DNA mismatch repair

Kelsey Aguirre Schilder

Erasmus MC, NL
Coordination of DNA mismatch repair by multiple state machines

Hien Le

University of Central Finland, FI
Qualitative and quantitative characterization of protein-protein and protein-DNA/small molecule interactions of MMR proteins with high-resolution mass-spectrometry-based tools

Dennis Winter

Chalmers University of Technology, SE
Gaining New Insight Into MMR Using Nanofluidic and Fluorescence Microscopy

Shiksha Saraogi

Justus Liebig University, DE
Dissection and Controlling the UvrD State Machine

Vaishnavi Bahulekar

PhD Student at Erasmus MC, Rotterdam, the Netherlands

Insight into the role of ATP hydrolysis during DNA mismatch repair initiation through biophysical and functional analysis

In my studies I aim to  understand the role of ATP hydrolysis and asymmetry of MutS state machine during mismatch repair.

About me

I am originally from Pune, India. I hold a master’s degree in biotechnology from Savitribai Phule Pune University (SPPU). Previously I was working as a Project assistant at IISER-Pune in Dr. Gayathri Pananghat’s lab where my work focused on biochemical characterization of bacterial cell division protein from a cell-wall less bacteria. In my spare time I like dancing and am trained Indian classical dancer.

My Ongoing Research 

Although various details regarding the structural and kinetic transitions of MutS have been unravelled, the precise role of ATP binding and hydrolysis in the asymmetric MutS dimer during these different conformational changes is not known. This is what I will be working on during my PhD studies.

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Department Molecular Genetics, Erasmus MC, Rotterdam, Netherlands

v.bahulekar@erasmusmc.nl

Margherita Fini

PhD Student at University of Bristol, UK

Symmetry and Asymmetry in Nucleotide Excision Repair of DNA

In my research I focus on the role of the dimeric UvrA ATPase in global and transcription-coupled nucleotide excision repair (NER)

About me

I’m Margherita Fini, a PhD student at the University of Bristol and a participant in the Repstate programme as a Marie Curie Early Career Fellow. As my name suggests, I’m Italian and I grew up in Florence, Tuscany. I obtained both my bachelor’s and master’s degrees at the University of Florence. My journey to get here began after completing my master’s degree, which I achieved with the highest grade of 110 cum laude in Molecular Biotechnology. During my studies, I engaged in scientific outreach activities in the field of molecular biology and completed two internships, each lasting six months, which resulted in the publication of two scientific articles that I co-authored. Following the completion of my studies, I spent nine months working in Paris. Initially, I was part of the Erasmus+ traineeship programme at the CNRS, and later I worked at the Gustave Roussy Institute. I’ve always had a passion for travel, architecture and theatre. Recently, I’ve taken up playing tennis to immerse myself more fully in British culture.

My Ongoing Research 

Currently, three DNA repair pathways involving the UvrABCD proteins have been suggested, with some proposed to be mutually exclusive. It is therefore of interest to ascertain whether and which of these models is accurate. In order to investigate these models, our focus will be on the UvrA protein, which plays a central role in all of them, but is suggested to engage in different interactions and perform varying functions within each.

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Khalid Rasheed

PhD Student at Justus Liebig University Giessen, DE

Function of the MutL state machine

In my studies I aim to identify (1) steps requiring ATP hydrolysis, (2) conformational transitions in MutL controlling complex formation with protein and DNA (3) the role of ATPase asymmetry, and (4) the underlying molecular mechanism.

 

About Me

My name is Khalid Rasheed. I am from India, where I first obtained my Bachelor’s degree in zoology and then a Master’s degree in zoology with specialization in genetics from Aligarh Muslim University. Next, I moved to France where I did M2 program in Gene Cell Development from University of Paris saclay and M2 project on BLM and CAF1 proteins and its role in double-stranded break repair from Institute Curie. My current research endeavors are focused towards advancing our understanding of the specific functions of MutL in DNA mismatch repair.
 

My Ongoing Research 

DNA mismatch repair (MMR) is a crucial cellular process that corrects errors in DNA replication and maintains genomic stability. The MutL protein plays a pivotal role in coordinating MMR reactions by facilitating ATP hydrolysis-dependent steps and interacting with various proteins and DNA substrates. Despite its significance, the precise structural and functional implications of MutL in the MMR pathway remain elusive. My project aims to unravel the role of ATP hydrolysis by MutL in orchestrating the timing, location, and directionality of DNA repair processes.

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Department of Biology and Chemistry, Justus Liebig University Giessen, Germany.

khalid.rasheed@chemie.bio.uni-giessen.de

 

Emma Arean-Ulloa

PhD Student at Leiden University Medical Center, NL

Unraveling the organization of the mismatch strand removal process

In my  studies I am trying  to reveal the molecular interaction between different proteins during the strand removal process through biochemical and structural methods.

Emma - Emma arean

About me

Originally from the Spanish region of Galicia, trekking through its stunning landscapes has always been one of my favorite outdoor activities. After graduating with a BSc in Biotechnology from the University of Salamanca in 2022, my journey through the world of scientific exploration began. Two enriching internships exposed me to different facets of research, from hands-on chemical synthesis in industry to the fundamental principles of basic research. My curiosity for structural studies led me to the National Centre for Cancer Research (CNIO) in Madrid.

There, I immersed myself in the fascinating mechanics of the mitochondrial replisome machinery. These experience gave me a great appreciation for the power of structural techniques. Determined to delve deeper, I pursued a Master’s degree in Biochemistry and Molecular Biology at the Complutense University of Madrid, graduating in July 2023. Now, since September 2023, I’ve embarked on an exciting PhD journey under the guidance of Dr Meindert Lamers.

My Ongoing Research 

My research project delves into the DNA mismatch repair process in E. coli. This intricate process involves the coordinated efforts of multiple proteins, including MutS, MutL, MutH, a DNA helicase, and a DNA exonuclease, to identify and remove mismatched nucleotides. However, the organization of these proteins’ sequential actions remains poorly understood. Therefore, my project aims to shed some light on the molecular interactions among these proteins during the strand removal process using mainly structural methodologies.

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Lamers Lab / DNA Replication & Repair, Department Cell and Chemical Biology, Leiden, the Netherlands

e.arean_ulloa@lumc.nl

Pratiksha Mall

PhD Student at Netherlands Cancer Institute, NKI, NL

Structure and Function of the MutSα and MutLα state machines

In my research I am aiming  to (1) define conditions that stabilize MutSα/MutLα complexes, (2) Solve cryo-EM structures of defined MutSα/MutLα states, (3) Use mutations to assess the effect of the ATPase cycle on activation of MutLα.  

About me

(to be added soon)

My Ongoing Research 

(to be added soon)

Abigail Jean Russel

PhD Student at University of Bristol, UK

Non-canonical roles for UvrD in DNA repair

In my  studies I am (1) exploring the role of UvrD in transcription and TC-NER; (2) investigating if UvrD resolves co-transcriptional R-loops; (3) studying UvrD:partner complexes, e.g. RNAP, UvrB, etc.

About me

I am from Cape Town, South Africa, where I had lived all of my life before moving to Bristol. I attended the University of Cape Town for all of my tertiary education. This included a BSc bachelors majoring in biochemistry and genetics, a BSc Honours in molecular and cell biology, and a MSc by research in molecular and cell biology. During my Honours and Masers I completed research projects working on the liquid-liquid phase separation properties of a malaria protein and two late embryogenesis abundant proteins from a resurrection plant, respectively. Outside of science, I love reading, dogs, and the beach. As a naturally competitive person, I am passionate about sport and love to play and watch as many as I can. I probably spend the most time enjoying football, but as a South African, rugby holds a special place in my heart.

My Ongoing Research 

My PhD project aims to further investigate the role of the helicase UvrD in bridging transcription and DNA repair. It builds on previous work in the group that discovered the interaction of RNA polymerase with UvrD, along with a hypothesized role of UvrD in R-loop regulation. This work will use a wide range of biochemical, structural, and biophysical approaches to investigate the mechanisms of UvrD within transcription-coupled nucleotide excision repair and R-loop homeostasis.

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School of Biochemistry, University of Bristol, UK.

email

Patrick Chirdon

PhD Student at University of Leeds, UK

Structural mass spectrometry for the analysis of nucleic-acid: protein interactions and applications in the study of DNA repair complexes

I am working on development of the novel approaches for HDX-MS of oligonucleotides as well as chemical and photo-crosslinking of DNA-protein contacts and exploration of the readouts of SHAPE analysis by advanced MS approaches, and development of  hydroxyl radical footprinting for oligonucleotide higher-order structure determination.

My Background

I’m from Cleveland, Ohio. I got my bachelor’s in biology from Case Western Reserve University and my master’s in biomedical engineering from Ohio University (Athens, Ohio). I also went through two years of medical school before I became an engineer. I worked for three years at a pharmaceutical company called Biosortia Microbiomics and a stock investing app called Echo Investing (launching this summer!). I like hiking, travel, meeting new people.

My Ongoing Research 

During my PhD I will deal with native MS/ion mobility and structural proteomics approaches (HDX-, XL- and covalent labeling MS). Those have found widespread use for studying protein complexes, however, their use to analyse interactions between proteins and DNA/RNA has been limited. We will extend these methods to DNA structure, and develop novel approaches for HDX-MS of oligonucleotides as well as chemical and photo-crosslinking of DNA-protein contacts. In addition, we will explore readouts of SHAPE analysis by advanced MS approaches, and develop hydroxyl radical footprinting for oligonucleotide higher-order structure determination (so far only available in the USA), in collaboration with Soft Matter beamline scientists at the Diamond synchrotron in Oxfordshire/UK.

Devendra Singh

Position 8: PhD Student at CNRS, France

Single-molecule characterization of transcription-coupled DNA repair

I am focusing on determining how the repair machinery successfully distinguishes the transcribed strand from the non-transcribed strand in the model bacterial system centered about the Mfd (“Mutation frequency decline”) protein and its downstream partners UvrA, UvrB, UvrC and UvrD.

About me

I am from India. My academic journey in biological sciences commenced with a Bachelor’s in Biochemistry and a Master’s in Biotechnology, from Aligarh Muslim University, India. I enriched my scientific skills during a 10 month M2 program in Fundamental Microbiology at the University of Paris Saclay, and research internship in Molecular and structural biology from Structural Cell Biology laboratory at Ecole Polytechnique, IP Paris. I am inherently passionate about research and scientific exploration, relishing engaging in scientific discussions with fellow enthusiasts. My tenure as a RepState PhD student at IBENS promises to be a significant chapter in my academic journey, where I aspire to broaden my scientific horizons and forge invaluable connections. While science fuels my intellect, I find solace and inspiration in the beauty of the Nature. My interests encompass exploring new places, rhythmic expression of poems, playing board games, and cricket.

My Ongoing Research 

My PhD project focuses on analyzing the composition of DNA repair complexes in real-time, focusing on the Transcription-coupled repair (TCR) mechanism. TCR efficiently corrects bulky DNA lesions located on the coding strand of genes and plays an important protective role against human aging and cancer. In order to unravel key aspects of this pathway, we are using single-molecule approaches like single-molecule nanomanipulation (magnetic trap) combined with single-molecule fluorescence (TIRF microscopy).

Aamna Sajid

PhD Student at CNRS, France

Single-molecule characterization of DNA mismatch repair

The composition and stoichiometries of the MMR complex as it progresses through its pathway remains poorly understood. The composition of the incision complex containing MutH remains unclear, and I am trying to determine the role and stoichiometry of the MutS and MutL components during this process

My Background

I’m Aamna Sajid from Pakistan. With a Bachelor’s degree in Biochemistry from Quaid i Azam University, Islamabad, and a subsequent Master’s in Biochemistry and Molecular Biology, my academic journey has been centered on understanding the intricacies of cancer genetics and genomics. During my Master’s my project focused on the mutation analysis of the TGFβ signaling pathway in pancreatic cancer. Beyond academia, I enjoy reading books and participating in parliamentary debates.

My Ongoing Research 

My project aims to characterize the dynamic stoichiometry of MutS, MutL, and MutH proteins in bacterial mismatch repair (MMR) complexes, which play a crucial role in eliminating replicative lesions in DNA. While the overall process is understood, the composition of MMR complexes during the reaction remains debated. The study will employ single-molecule techniques to monitor real-time assembly and action of MMR complexes on DNA mismatches, utilizing the specific characteristics of the E. coli system, where MutH incises at GATC sites. By reconstructing MMR reactions using fluorescently-labeled proteins and single-molecule fluorescence detection, the research seeks to observe catalytic events and fluorescence emitted by the components, providing insight into the composition and stoichiometry of MMR complexes throughout the repair reaction.

Kelsey Aguirre Schilder

PhD Student at ErasmusMC, NL

Coordination of DNA mismatch repair by multiple state machines

In my research my goals are to understand how the complete MMR reaction is coordinated in humans:

  • Study MutSα and MutLα ATPases coordinate repair and how directionality is achieved.
  • Investigate the regulation of ExoI by MutSα, MutLα and RPA.

About me

My name is Kelsey and I’m from Almería, south of Spain. I earned my Bachelor’s degree in Biochemistry and my master’s degree in Biotechnology, both from the University of Granada (Spain). During my studies, I developed a great interest in molecular biology and became passionate about laboratory research. After that, I spent two months at the University of Groningen, where I learnt about peptide engineering. Following this, I returned to Spain to work in the Department of Biochemistry and Molecular Biology II at the University of Granada, continuing the research I started in my master’s thesis, working on finding alternatives for the treatment of infections caused by the pathogenic strain Pseudomonas aeruginosa.  Now, I am really excited to continue my academic journey with this PhD.

My Ongoing Research 

My research projects centers on human mismatch repair, a crucial cellular mechanism that maintains genome integrity. During DNA replication, errors such as base mismatches or small insertions and deletions can occur, mismatch repair identifies and corrects these errors. My work focuses on how exonuclease I is regulated by MutSα, MutLα, and RPA, and the main objective of this work is to reconstitute the complete repair pathway to elucidate how the coordinated actions of these individual proteins result in efficient DNA repair.

Thi-Kim-Hien Le

PhD Student at UEF, Finland

Qualitative and quantitative characterization of protein-protein and protein-DNA/small molecule interactions of MMR proteins with high-resolution mass-spectrometry-based tools

We aim to determine the stoichiometries, interactions and interfaces of these complexes, as well as their conformational spectra, ligand interactions and how these change in different nucleotide-bound states.  

About me

I am from Vietnam and I have studied a major in Analytical Chemistry. Afterwards, I attended the Erasmus Mundus joint master’s programme EACH (Excellence in Analytical Chemistry), at Tartu University and Uppsala University.

My Ongoing Research 

I have started my research very recently. More information will appear here soon!

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Bio-organic Chemistry
Research group, 
Department of Chemistry, Faculty of Science, Forestry and Technology, University of Eastern Finland, Joensuu, Finland.

hien.le@uef.fi

Dennis Winter

PhD Student at Chalmers University of Technology, Sweden

Gaining New Insight Into MMR Using Nanofluidic and Fluorescence Microscopy

We are trying to get a better understanding of the DNA mismatch repair (MMR) system of E. coli.

About me

I am originally from Germany. I did both my bachelor’s and master’s degrees at the University of Applied Sciences in Biberach. During this time, I did internships in Sweden at Uppsala

University and at NTNU in Trondheim, Norway. I am now doing my PhD at Chalmers University in Gothenborg, Sweden, on the topic of DNA mismatch repair using nanofluids and fluorescence microscopy. In my spare time I enjoy climbing, hiking and reading.

My Ongoing Research 

The aim of my project is to gain a better understanding of the DNA mismatch repair (MMR) system of E. coli. The MMR is responsible for replacing wrongly incoperated Watson-Crick base pairs, reducing the mutation rate by 100-1,000-fold. This project will use nanofluidics, fluorescence microscopy and optical tweezers to visualise and study the proteins involved in real time.

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Westerlund’s BioNanoFluidics Lab, Chemical Biology, Life Sciences, 
Chalmers University of Technology, Gothenburg, Sweden.

denniswi@chalmers.se

Shiksha Saraogi

PhD Student at JLU, Germany

Dissection and Controlling the UvrD State Machine

We aim to identify (1) steps and structural changes required in UvrD and the DNA substrates, (2) determine key conformational states and their transitions in UvrD which might be controlled by interaction partners, and (3) control the conformational states in UvrD using permanent or transient (caged/photo switchable) crosslinks and/or protein complex formation. 

About me

I am originally from the vibrant city of Bangalore, India. My journey in the world of science began with a Bachelor’s degree in Biotechnology from the Manipal School of Life Sciences, where I delved deep into the fascinating realm of biological exploration. Eager to expand my horizons, I pursued a Master’s degree in Biomedical Sciences with a specialisation in Oncology from the University of Amsterdam, diving into the complex field of cancer research with fervour. When I’m not immersed in the lab, I often shoot hoops on the basketball court, capture breathtaking moments through my camera lens (@shiksha.jpg), embark on exciting travel adventures, or experiment with flavours in the kitchen. With a curious mind and a zest for life, I’m constantly seeking new opportunities to learn, grow, and make meaningful contributions to the world around me.

My Ongoing Research 

My project is about UvrD. UvrD in E. coli helps fix mistakes in the DNA by recognising and untangling strands that have errors, like mismatched base pairs. This allows other proteins to come in and clean up the mistake made before the DNA is put back together. UvrD’s job as a helicase, which unwinds the DNA, is crucial for starting this repair process, making it important for keeping the DNA healthy. However, UvrD does not operate alone; it collaborates with a multitude of other proteins involved in DNA repair, such as MutL and MutS. This collaborative effort can be likened to UvrD being a part of a team that orchestrates and executes the repair work in the DNA, highlighting the importance of teamwork in our research. To better understand how UvrD works and changes shape during these repairs, I will use techniques like fluorescence-based assays, single-molecule studies, and mass spectrometry. These methods will help me see how UvrD moves and behaves, giving a clearer picture of its role in fixing DNA mistakes.

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Institute of Biochemistry, Department of Biology and Chemistry, Justus Liebig University Giessen, Germany.

shiksha.saraogi@chemie.bio.uni-giessen.de

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