Project Choices Scheme at King's College London Summer 2021 - King's College London
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Wellcome Trust Biomedical Vacation Scholarship
Scheme at King’s College London
Project Choices
Summer 2021TABLE OF CONTENTS:
Cellular and Developmental Science
2021_01 Identification of genes required for axon guidance in Drosophila. .................................................................. 4
2021_02 Artificial Evolution on a Digital Microfluidic Device ........................................................................................ 5
2021_03 Investigating microRNA regulation of immune cell development, function and metabolism. ........................... 6
2021_04 Following fate changes during Otitis media (glue ear) in a mouse model ........................................................ 7
2021_05 Identifying regulators of muscle stem cell development and function ........................................................... 8
Genetics and Molecular Science
2021_06 Liquid biopsy in pancreatic cancer: from cancer screening to therapy effecacy and personalized medicine . 9
2021_07 CRISPR gene-editing technology: A magic bullet or a nuclear bomb? ............................................................ 10
2021_08 Genetics of Thyroid Cancer: Assessing Sequencing Data for Known and Novel Causative Genes .................... 11
2021_09 Characterising and targeting the DNA G-quadruplex ................................................................................... 12
2021_10 HDX-MS to study receptor and antibody interaction of the Spike of B.1.1.7 (U.K.) SARS-CoV-2 variant ......... 13
Infection and Immuno biology
2021_11 The function of CD20 during initial steps of human B cell activation. ............................................................ 14
2021_12 In vivo imaging of lung epithelial permeability to study the anti-inflammatory properties of macrolides .....15
2021_13 The investigation into the mechanism for DNA capture and transport by topoisomerase II using high-
resolution structure determination. ......................................................................................................................... 16
Page 2 of 232021_14 Cutting it long and short; influenza viral mechanism to inhibit host gene expression ....................................17
Neuroscience and Mental Health
2021_15 Interhemispheric connectivity of the supplementary motor area in infants with Congenital Heart Disease . 18
2021_16 Are 'neurotypical' controls really neurotypical? The impact of sub-clinical mental health traits on cognitive
outcomes .................................................................................................................................................................. 19
2021_17 Solving Foxg1 syndrome using zebrafish genetic models ............................................................................... 20
2021_18 Investigating the effects of Tryptophan loading on attention and impulsivity in individuals with ADHD. ....... 21
2021_19 Validation of transgenic mouse model for pain research ............................................................................. 22
Physiology
2021_20 Measurement of fluid intake from muscle activities ................................................................................... 23
Page 3 of 232021_01 Cellular and developmental science
Identification of genes required for axon guidance in Drosophila.
Supervisor: Prof. Guy Tear guy.tear@kcl.ac.uk
Website: https://devneuro.org/cdn/group-overview.php?groupID=28
https://www.kcl.ac.uk/people/guy-tear
Affiliated Lab: Prinicipal Investigator - Molecular mechanisms of axon guidance
Campus: Guy's;
Aims and Research Questions of the Project:
To characterise the cellular phenotypes in a collection of Drosophila mutants that have been identified as defective
in their ability to form the CNS to identify those where axon guidance is specifically disrupted. To map the location of
the mutations within the Drosophila genome.
Prerequisite Skills or Academic Background Required:
Suitable for all bioscience students
Page 4 of 232021_02 Cellular and developmental science
Artificial Evolution on a Digital Microfluidic Device
Supervisor: Prof. Mark Wallace mark.wallace@kcl.ac.uk
Website: http://markwallace.org/
https://www.kcl.ac.uk/people/mark-wallace
https://www.kcl.ac.uk/research/wallace
Affiliated Lab: Principal Investigator - Artificial Membrane & Cell Mimics
Campus: Guy's;
Aims and Research Questions of the Project:
Can we create artificial life on an electronic chip? Perhaps not just yet, but this project will take the first steps to
creating artificial self-replicating systems. These will be based on electronic control of aqueous droplets in a digital
microfluidic device. We will link artificial cell division with multiple cycles of replication of biological material, thus
starting to probe the natural version of this process: evolution. You will use optical microscopy alongside software
programming to control an EWOD (electrowetting on dielectric) device to manipulate the droplets. We will aim to
develop cycling protocols required to mimic the evolution process.
Prerequisite Skills or Academic Background Required:
This is a practical project at the interface of biology, chemistry and physics, requiring only good general lab skills.
Page 5 of 232021_03 Cellular and developmental science
Investigating microRNA regulation of immune cell development,
function and metabolism.
Supervisor: Dr Luke Roberts luke.roberts@kcl.ac.uk
Website: https://www.kcl.ac.uk/people/anna-schurich
https://www.kcl.ac.uk/people/dr-luke-roberts-1
Affiliated Lab: Post doctoral researcher with Dr Anna Schurich supervising the project
Campus: Guy's;
Aims and Research Questions of the Project:
The immune system plays numerous essential roles in the body, including protection from invading pathogens and
directing important processes such as tissue repair. Conversely, numerous forms of disease are connected to
immune system responses that are acting ‘incorrectly’. MicroRNAs are small, non-protein-coding nucleic acids that
are critical in directing how genes are expressed. As such, microRNAs are essential regulators of how cells develop
and function. Using a wide range of cellular and molecular biology techniques, this project aims to investigate how
processes such as the development, function, and metabolism of immune cells are regulated by microRNAs.
Prerequisite Skills or Academic Background Required:
The student will ideally have a foundational understanding of differences between the major immune cell types and
their roles in the immune response.
Page 6 of 232021_04 Cellular and developmental science
Following fate changes during Otitis media (glue ear) in a mouse model
Supervisor: Dr Natalie Milmoe natalie.milmoe@kcl.ac.uk
Website: https://www.kcl.ac.uk/research/tucker-lab-fodocs
https://www.kcl.ac.uk/people/natalie-milmoe
Affiliated Lab: Post-doctoral fellow within Professor Abigail Tucker's craniofacial development laboratory
Campus: Guy's;
Aims and Research Questions of the Project:
Otitis media (OM), or glue ear, is an extremely common disease associated with the middle ear. For many children,
repeated inflammations of the lining of the middle ear cause hearing problems, impacting on speech and language
development, and in severe cases lead to permanent hearing loss. We aim to follow the development of otitis media
using a mouse model of a human syndrome with a high incidence of chronic OM, the Eya1 mouse. We will
investigate how the mucosa responds as chronic OM develops, looking for changes to cell identity using transgenic
reporter mice.
Prerequisite Skills or Academic Background Required:
Project will be most suitable for undergraduates from a biology, biochemistry or a biomedical sciences course
Page 7 of 232021_05 Cellular and developmental science
Identifying regulators of muscle stem cell development and function
Supervisor: Dr Robert Knight robert.knight@kcl.ac.uk
Website: https://www.kcl.ac.uk/research/knight-group
Affiliated Lab: Principal Investigator - muscle regeneration
Campus: Guy's;
Aims and Research Questions of the Project:
During development and regeneration muscle stem cells (muSCs) generate muscle fibres. Some of these progenitor
cells do not differentiate into myofibres after proliferation but become quiescent. How this choice is made is of
intense interest as it may explain why muscle regeneration is ineffective in several diseases and in ageing. This
project aims to visualise this process in a living animal using laser microscopy to track and characterise muSCs during
muscle formation in zebrafish larvae. We will investigate whether candidate signalling pathways control muSC fate
choice and muscle formation using microscopy, molecular genetics, immunolabelling and pharmacological
manipulations.
Prerequisite Skills or Academic Background Required:
this project is suitable for hard working, dedicated students with an interest in cell biology
Page 8 of 232021_06 Genetics and molecular science
Liquid biopsy in pancreatic cancer: from cancer screening to therapy
effecacy and personalized medicine
Supervisor: Dr Alessandra Vigilante alessandra.vigilante@kcl.ac.uk
Website: https://www.kcl.ac.uk/lsm/research/divisions/gmm/departments/stemcells/people/dr-
alessandra-vigilante
Affiliated Lab: Principal investigator - Bioinformatics
Campus: Guy's;
Aims and Research Questions of the Project:
Liquid biopsy is a non-invasive method that can be used in cancer screening and treatment to detect mutations and
evaluate tumour heterogeneity. Blood contains different types of biological materials like circulating cells, platelets
and cell-free DNA (cfDNA). In cancer patients, circulating tumour DNA (ctDNA) is composed of DNA released by
tumour cells and it may carry the same genomic aberrations and mutations as the primary tumour and/or
metastases and can be used to screen for tumour-derived mutations. Tumour-specific mutations in ctDNA sequence
can operate as a new type of cancer biomarker and help to identify cancer patients from a group of healthy
individuals. In collaboration with Genomix4Life srl, we obtained the liquid biopsy of patients with metastatic
pancreatic cancer where blood was drawn at diagnosis (T0) and different time points (T1-T2-T3) from the beginning
of the immunotherapy. We propose to examine ctDNA mutations with other biomarkers (e.g. methylation) to
implement a bioinformatics pipeline able to analyse and integrate further data for an improved classification model
of disease progression, therapy effectiveness and possible onset of resistance.
Prerequisite Skills or Academic Background Required:
none listed
Page 9 of 232021_07 Genetics and molecular science
CRISPR gene-editing technology: A magic bullet or a nuclear bomb?
Supervisor: Mr Dongchan Choi dongchan.choi@kcl.ac.uk
Website: https://www.franziskadenk.com/research
Affiliated Lab: PhD student within Dr Franziska Denk's Molecular Pain Research laboratory.
Campus: Guy's;
Aims and Research Questions of the Project:
Chronic pain is a major issue affecting approximately 20% of people world-wide. That is 1 BILLION individuals!
Currently, no effective treatments exist. Our lab is exploring gene editing as a novel approach. We are targeting a
gene called Scn9a, mutations in which make people completely pain-free. We would like you to help us assess how
safe this treatment is by looking for off-target effects. We want to treat sensory nerves but need to check whether
we have not inadvertently affected other organs. You will perform antibody staining on mouse tissue and learn lots
of interesting things about pain in the process!
Prerequisite Skills or Academic Background Required:
Basic understanding of antibody binding. Calculations involving concentrations. Basic laboratory skills such as
pipetting.
Page 10 of 232021_08 Genetics and molecular science
Genetics of Thyroid Cancer: Assessing Sequencing Data for Known and
Novel Causative Genes
Supervisor: Prof. Emma Duncan emma.duncan@kcl.ac.uk
Website: n/a
Affiliated Lab: Principal Investigator - Endocrine Genetics
Campus: St Thomas';
Aims and Research Questions of the Project:
This project will assess a cohort of individuals at high risk of familial thyroid cancer, to determine if they have
mutations in any of the known cancer syndrome genes associated with thyroid cancer - or whether they carry a
variant in a novel thyroid cancer gene.
Prerequisite Skills or Academic Background Required:
Ability to use Microsoft Excel
Page 11 of 232021_09 Genetics and molecular science
Characterising and targeting the DNA G-quadruplex
Supervisor: Dr Natasha Rhys natasha.rhys@kcl.ac.uk
Website: https://nms.kcl.ac.uk/lorenz.lab/wp/
https://kclpure.kcl.ac.uk/portal/natasha.rhys.html
Affiliated Lab: Postdoctoral Fellow within Professor Chris Lorenz's Computational Biophysics Group
Campus: Strand;
Aims and Research Questions of the Project:
G-quadruplexes are an intriguing nucleic acid secondary structure formed in guanine-rich areas. They have gained
much interest for their role in cancer and have consequently become a major focus for DNA-targeted therapies.
Targeting them requires a comprehensive understanding of the topology and characteristics of these structures. This
project will use Molecular Dynamics simulations to explore the structure and properties of quadruplexes relevant to
the cancer field to identify factors that will allow DNA-targeted therapeutics to be determined.
Prerequisite Skills or Academic Background Required:
none listed
Page 12 of 232021_10 Genetics and molecular science
HDX-MS to study receptor and antibody interaction of the Spike of
B.1.1.7 (U.K.) SARS-CoV-2 variant
Supervisor: Dr Valeria Calvaresi valeria.calvaresi@kcl.ac.uk
Website: http://politislab.com
https://www.kcl.ac.uk/research/politis
Affiliated Lab: Post-doctoral fellow within Politis Lab
Campus: Guy's;
Aims and Research Questions of the Project:
The spread of the more infectious SARS-CoV-2 variant B.1.1.7 is a serious threat to public health. Mutations on the
Spike of this new variant are thought to confer higher affinity of the Spike to its human receptor ACE2, thus higher
infectiveness to the virus. Here, we will use hydrogen-deuterium exchange mass spectrometry (HDX-MS) to study, at
molecular level, the interaction of the Spike of the B.1.1.7 to ACE2. Another key aim is investigating whether and
how antibodies from patients infected by the original virus recognize the Spike of the B.1.1.7, enabling important
new knowledge for contrasting the spread of COVID-19.
Prerequisite Skills or Academic Background Required:
This project will be suitable for students with a background in Protein Chemistry, Biochemistry, Pharmacy and
Structural Biology.
Page 13 of 232021_11 Infection and immuno-biology
The function of CD20 during initial steps of human B cell activation.
Supervisor: Dr Anna Bajur anna.bajur@kcl.ac.uk
Website: https://www.katelynspillanelab.org/
Affiliated Lab: Post-doctoral fellow within Doctor Katelyn Spillane's Immune Cell Mechanics Laboratory.
Campus: Guy's;
Aims and Research Questions of the Project:
Antibodies defend us against infection by binding to viruses and microbial toxins, thereby inactivating them. The
initial step leading to the successful production of neutralizing antibodies is recognition of antigen by B cells.
Therefore, it is important to understanding what triggers it. CD20, one of the B cell membrane proteins is an
outstanding target for anti-tumour immunotherapy, yet its function in B cells remains elusive. The aim of this
project will be to investigate the role of CD20 during early B cell activation events including calcium signalling and
immune synapse formation in response to antigens.
Prerequisite Skills or Academic Background Required:
This project will be most suitable for biology and chemistry students but should be accessible for students with
physics background as well.
Page 14 of 232021_12 Infection and immuno-biology
In vivo imaging of lung epithelial permeability to study the anti-
inflammatory properties of macrolides
Supervisor: Dr Francis Man francis.man@kcl.ac.uk
Website: https://www.kcl.ac.uk/lsm/research/divisions/ips/research/major-research-
themes/sacklergroup/index
https://kclpure.kcl.ac.uk/portal/francis.man.html
Affiliated Lab: 1: Prof Clive Page - Sackler Institute of Pulmonary Pharmacology; 2: Dr Francis Man - Research
Fellow in Prof Clive Page's lab; 3: Dr Rafael Torres Martin de Rosales (Imaging Chemistry and
Biology, St Thomas campus)
Campus: St Thomas';Waterloo;
Aims and Research Questions of the Project:
Macrolide antibiotics inhibit inflammation and protect the lung epithelium in asthma and COPD, but their long-term
use leads to bacterial resistance. Novel, non-antibiotic macrolides could overcome this issue and reduce
inflammatory exacerbations in patients, but have mainly been tested in vitro to date. PET imaging of lung epithelial
permeability could provide a non-invasive way of assessing the barrier-promoting properties of these novel
macrolides. This project will investigate the use of radiolabelled nanoparticles as markers of lung epithelial
permeability. The student will label nanoparticles with the PET radionuclide 89Zr and perform in vivo imaging in a
mouse model of lung inflammation.
Prerequisite Skills or Academic Background Required:
This project is suitable for any student with a background in biomedical sciences.
Page 15 of 232021_13 Infection and immuno-biology
The investigation into the mechanism for DNA capture and transport
by topoisomerase II using high-resolution structure determination.
Supervisor: Dr Mark R. Sanderson mark.sanderson@kcl.ac.uk
Website: https://www.kcl.ac.uk/people/mark-sanderson
Affiliated Lab: 1. Principal Investigator - Structural Biology
Campus: Guy's;
Aims and Research Questions of the Project:
Type II topoisomerases perform essential roles in DNA replication, chromosome segregation, and recombination
and are important antibacterial and anticancer targets. Topoisomerase IIs regulate DNA supercoiling and
chromosome segregation via an ATP-driven DNA strand passage mechanism. However, the paucity of structures for
native full-length proteins has been a significant obstacle in defining the reaction pathway. We solved the first high
resolution X-ray crystal structure of an ‘open clamp’ complex of a topoisomerase II. In this project we wish to trap in
addition to G-gate DNA, T-gate DNA in the ATPase domain and solve the structure of this complex.
Prerequisite Skills or Academic Background Required:
Biochemistry and have studied protein structure and function modules in the second year
Page 16 of 232021_14 Infection and immuno-biology
Cutting it long and short; influenza viral mechanism to inhibit host
gene expression
Supervisor: Dr Stuart McKellar stuart.mckellar@kcl.ac.uk
Website: https://www.kcl.ac.uk/research/mischo-lab
Affiliated Lab: Post-doctoral fellow within Dr Hannah Mischo’s Regulatory Modulation of Transcription
Termination laboratory.
Campus: Guy's;
Aims and Research Questions of the Project:
Our lab studies how influenza A virus (IAV) overcomes the innate defences of its infected host cell. Through multiple
mechanisms, IAV prevents cellular recognition of transcription termination signals in host pre-mRNAs and so inhibits
gene expression and subsequent antiviral responses. A prospective student would purify viral proteins and test their
ability to inhibit transcriptional termination in an established in vitro system. The student will also be able to verify
their results in vivo through heterologous viral protein expression to examine their effects on host anti-viral gene
expression. This defined project will provide broad experimental training in a topical infectious diseases background.
Prerequisite Skills or Academic Background Required:
This project is suitable for students of all biological disciplines relating to molecular and cellular biology including
virology, immunology, genetics, and biochemistry.
Page 17 of 232021_15 Neuroscience and mental health
Interhemispheric connectivity of the supplementary motor area in
infants with Congenital Heart Disease
Supervisor: Dr Alexandra Bonthrone alexandra.bonthrone@kcl.ac.uk
Website: https://www.kcl.ac.uk/people/serena-counsell
https://kclpure.kcl.ac.uk/portal/alexandra.bonthrone.html
Affiliated Lab: Post-doctoral researcher within Professor Serena Counsell’s research group examining brain
development in infants with Congenital Heart Disease.
Campus: St Thomas';
Aims and Research Questions of the Project:
Congenital Heart Disease (CHD) is the most common congenital abnormality, affecting approximately 1% of births.
Up to 50% of children with CHD are diagnosed with neurodevelopmental impairments, including motor coordination
difficulties. The supplementary motor area (SMA) is a region within the brain implicated in sequencing of
movements. The aim of this project is to assess whether microstructural development of white matter fibres
connecting the left and right supplementary motor areas in 60 neonates with Congenital Heart Disease is impaired
relative to matched healthy controls.
Prerequisite Skills or Academic Background Required:
none listed
Page 18 of 232021_16 Neuroscience and mental health
Are 'neurotypical' controls really neurotypical? The impact of sub-
clinical mental health traits on cognitive outcomes
Supervisor: Dr Caroline Catmur caroline.catmur@kcl.ac.uk
Website: https://kclpure.kcl.ac.uk/portal/caroline.catmur.html
http://sites.google.com/site/carolinecatmur/
Affiliated Lab: Principal Investigator - Social Cognitive Neuroscience
Campus: Guy's;
Aims and Research Questions of the Project:
The project aims to investigate how sub-clinical mental health traits, in particular traits of depression and anxiety,
distribute in a large neurotypical population. An initial analysis of a limited dataset (N = 400) revealed higher
frequencies of medium-to-high depressive and anxious traits in a neurotypical population. This project aims to
replicate this effort in a larger, more representative population; and to investigate the effects of these traits on
performance on standardised cognitive tasks, with the overall aim of understanding how sub-clinical mental health
traits affect performance across a range of cognitive abilities.
Prerequisite Skills or Academic Background Required:
none listed
Page 19 of 232021_17 Neuroscience and mental health
Solving Foxg1 syndrome using zebrafish genetic models
Supervisor: Prof. Corinne Houart corinne.houart@kcl.ac.uk
Website: https://devneuro.org/cdn/group-overview.php?groupID=16
Affiliated Lab: Principal Investigator - Developmental Neurobiology and neurodevelopmental disorders
Campus: Guy's;
Aims and Research Questions of the Project:
FOXG1 is a transcription factor critical for forebrain development in all vertebrates. Heterozygous mutations in its
gene cause FOXG1 syndrome, a severe neurodevelopmental disorder characterised by seizures, coordination
impairment and intellectual disabilities affecting patients from birth. We have a limited understanding of Foxg1
functions and no therapeutic avenues to help the patients. We use a zebrafish genetic model of FOXG1 syndrome to
understand the developmental progression of the disorder. The project aims to analyse the model further and
participate to a screen for pharmacological compounds modifying the brain pathologies.
Prerequisite Skills or Academic Background Required:
This project is suitable for second and third year Biology undergraduates with some knowledge of neuroscience.
Page 20 of 232021_18 Neuroscience and mental health
Investigating the effects of Tryptophan loading on attention and
impulsivity in individuals with ADHD.
Supervisor: Dr Ellie Dommett eleanor.dommett@kcl.ac.uk
Website: The lab does not have a website (we have a social media presence)
The PI Pure page is: https://kclpure.kcl.ac.uk/portal/eleanor.dommett.html
Affiliated Lab: Principal Investigator - Non-drug treatments in Attention Deficit Hyperactivity Disorder
Campus: Guy's;
Aims and Research Questions of the Project:
Attention Deficit Hyperactivity Disorder (ADHD) is characterised by poor attention, impulsivity and hyperactivity.
Although considered a childhood disorder, adults have ADHD and are under-represented in research. First-line
treatment for adult ADHD is psychostimulants but they are associated with various problems meaning alternatives
must be investigated. Research shows reduced depletion of the dietary precursor for serotonin (tryptophan) is
associated with ADHD-like behaviours. However, few studies have investigated how tryptophan impacts adult ADHD,
and the effects on symptoms is unknown. We will investigate the effects of tryptophan on attention and impulsivity
in adults with ADHD, to establish treatment-potential.
Prerequisite Skills or Academic Background Required:
This project would be suitable for Psychology or Neuroscience undergraduates but may also be appropriate for
medicine/related disciplines if they have some statistical training.
Page 21 of 232021_19 Neuroscience and mental health
Validation of transgenic mouse model for pain research
Supervisor: Dr Sara E. Jager sara.jager@kcl.ac.uk
Website: https://www.franziskadenk.com
https://www.kcl.ac.uk/people/franziska-denk
Affiliated Lab: Post-doctoral fellow within Dr Franziska Denk's Chronic Pain lab
Campus: Guy's;
Aims and Research Questions of the Project:
Neuropathic pain is a chronic condition seen in patients suffering a direct injury to the peripheral or central nervous
system or an indirect injury due to, e.g., diabetes. Current treatment options fall short of preventing or completely
relieving patients of their pain. To help develop better treatment options we need to further our understanding of
neuropathic pain. Most research have focused on the neurons, but in this project, we will validate a transgenic
mouse model which will be used to explore the satellite glial cells’ involvement. Future research with this model will
hopefully lead to better treatment options.
Prerequisite Skills or Academic Background Required:
none listed
Page 22 of 232021_20 Physiology
Measurement of fluid intake from muscle activities
Supervisor: Dr Ernest Kamavuako ernest.kamavuako@kcl.ac.uk
Website: https://www.kcl.ac.uk/people/ernest-kamavuako
Affiliated Lab: Laboratory for Prosthetics and Health Engineering
Campus: Strand;
Aims and Research Questions of the Project:
The main scope of this project is to develop a system which will be capable of accurately quantify the daily fluid
intake of adults aged 65 and over automatically, thus lifting the burden for nurses and cares who will not need to
rely on manual methods, that are often prone to misreporting, while also allowing them to rapidly intervene before
dehydration occurs. To accomplish this, the plan is to use a combination of sensors, namely surface
electromyographic sensors, microphones and accelerometers to detect signals originated from swallowing activities.
Prerequisite Skills or Academic Background Required:
Requires some knowledge of matlab programming
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