2023 Summer Research Placements

We are now closed for new project proposals. We will open for the next round in November 2023.

Placements are for 8-weeks (July-August 2023) and are available for students in their second year of study at one of the following institutions.

• Kingston University
• London South Bank University
• London Metropolitan University
• Middlesex University
• University of Roehampton
• University of East London
• University of West London
• University of Westminster
• University of Hertfordshire
• University of Bedfordshire

The projects offered are designed to provide direct and relevant research experience to undergraduate students. Previous experience is not required, only enthusiasm, commitment to the duration of the project, and the intention to learn.

During the placement, successful students will also have the opportunity to attend training and social opportunities within the LIDo Doctoral Training Programme. This will give direct access to our PhD students and provide the opportunity to experience a PhD programme environment first-hand. Who knows, maybe you’ll decide that a PhD is the next step in your academic career!

Students will receive a salary at the London Living Wage level based on a full-time working week of 36 hours, ongoing dedicated lab supervision as well as a LIDo PhD student ‘buddy’ to help you make the most of your experience. The placement will end with a presentation afternoon.

You can apply for as many projects as you wish, so don’t be afraid to consider topics outside your main areas of interest. We require a separate application for each project you’re interested in and recommend tailoring your answers to each project.

Successful students must be available to attend a mandatory pre-placement briefing (online) on Monday 12th June from 12:00-14:00.

CLICK HERE TO DOWNLOAD THE APPLICATION FORM

Application forms must be returned to LIDo.Admissions@ucl.ac.uk by 5pm on Monday 24th April 2023. Late submissions of applications are not permitted and all applications must be accompanied by interim transcripts of your grades so far. 

Examining the role of yif1a in receptor trafficking and dendritic spine remodeling – Dr. Adele Leggieri (Queen Mary, University of London)

Mental health influences how people think, feel, and behave, therefore representing a worldwide major concern. Environmental and genetic factors can both impair an individual's mental health, increasing the risk of developing such disorders. This project aims to identify these genetic factors as well as potential therapeutic targets.

Question: does yif1a loss of function disrupts neurotransmitter receptor trafficking to dendritic spines?

Significance: variations in yif1a are associated with mental disorders such as autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and obsessive-compulsive disease (OCD). Mental disorder represents a significant economic and social burden, affecting 1 in every 8 people in 2019. OCD is the fourth most common psychiatric disorder and is among the 20 top causes of mental illness for people between the ages of 14 and 44. The estimated global prevalence of children affected by ASD and ADHD is 1% and 5% respectively, and the prevalence of ADHD in people already affected by ASD ranges from 50% to 70%. Although the role of YIF1A in the etiology of psychiatric disease is still unknown, YIF proteins play a key role in protein trafficking. YIF1A paralogue, YIF1B, is known to traffic serotonin receptors to dendritic spines, suggesting that YIF1A may also be involved in neuroreceptor trafficking. As disruption in serotonin and dopamine signaling is common in psychiatric disorders, mutations in YIF1A may disrupt trafficking of receptors within these pathways. Identify the cellular role of YIF1A might lead to identification of new therapeutic targets.

Experimental plan: the student will use a CRISPR-Cas9 loss of function (LoF) yif1a zebrafish line available within the laboratory. Zebrafish (Danio rerio) is a powerful model in biomedical research: 84% of the gene associated with human psychiatric disease have a zebrafish counterpart, and zebrafish show conservation of the main human neural circuits, including dopaminergic and serotoninergic systems. To test the hypothesis that yif1a is involved in serotonin and/or dopamine trafficking/anchorage to dendritic spines (1) bioinformatic analysis will be used to examine potential protein-protein interactions between yif1a and members of the dopaminergic and serotoninergic receptors families, (2) antibodies that recognize zebrafish dopamine and serotonin receptors will be used in immunohistochemical analysis to explore the neuronal localization of receptors subtypes. Stained sections will be examined using high resolution confocal microscopy. (3) Furthermore, to test impact of yif1a LoF on serotonin/dopamine regulated behavior, the student will perform behavioral experiments in the presence and absence of serotonin/dopamine receptors agonists and antagonists.

This project, including both wet (cell biology, molecular biology, histology) and dry (R programming language and biostatistics) laboratory techniques, aim to provide the student with a great opportunity to gain knowledge in different fields. In addition, due to the translational relevance of the project, the student will also learn how such an animal apparently different from human architecture, can help in understanding the basis of human disease. Thus, the student will also learn fish brain anatomy and how to analyze behavioral phenotypes using R programming language.

Predicting emergence of resistance by integrating genomic and transcriptomic profiles of pathogens – Dr Arundhati Maitra (University College London)

Bacterial reference strains, unexposed to drugs, exhibited resistance towards them in our previous studies. The project will use this data and further analyse preserved samples to dissect the role of gene expression changes in the acquisition of resistance. This will expand our understanding of the spontaneous variability in pathogens and adaptations to survive external stresses.

The Scientific Question- What is the underlying mechanism that allows a sub-population of unexposed bacteria to survive antimicrobial pressure – spontaneous gene mutations or changes in gene expression profiles or both? Armed with this knowledge, can we predict the rise of resistance?

Why is it important? Antimicrobial resistance is a global health issue. A deeper understanding of the mechanisms that allow the acquisition of resistance would enable identification of drug combinations that can effectively inhibit them.

Experimental Approach

Weeks 1-2:

• Literature survey to gain a robust understanding of the pathogen, its pathogenesis, the drugs being investigated in this study, their mechanism of action and the known mechanisms for resistance against them.
• Genome-wide search of E. coli to list out the relevant genes for hetero-resistance – relevant SNPs in resistance genes, promoter sites, transcriptional regulators and compensatory mutations, efflux pumps, etc.
• Designing and ordering the primer/probe sets for qPCR for the selected genes.

Weeks 3-5:

• Samples showing resistance have already been sequenced by the PGU. This data (16 samples), which is in the raw-read format, will need to be analysed for the presence of relevant SNPs through variant calling using existing pipelines.
• All 16 samples were also cryo-preserved at the time of the original experiment. RNA from these samples will be extracted to perform multiplex qPCR on selected genes or sent for RNAseq at the Pathogen Genomics Unit to detect whether they are regulated at the transcriptional stage.
• Bacteria from the samples will be tested for their antimicrobial susceptibility profile to confirm previous results.

Week 6-8:

• Identify transcriptomic marker(s) by evaluating the up and down regulation of relevant genes with existing pipelines using data from the qPCR/RNA seq experiments.
• Using the data from the static experiments as a training set, compare the predictive performance of the candidate genomic, transcriptomic or combined marker using data from the HFIM experiments.
• The student will present their finding in the lab group meeting at the end of the project.

The student will get to work on a well-structured, interdisciplinary project. They will analyse ‘omics data, be trained in micro- and molecular biology, develop critical-thinking and presentation skills. They will also be supported by Dr Frank Kloprogge (IGH) and Prof TimMcHugh (Director, CCM) whose expertise and interests include infectious diseases, AMR and PKPD modelling. Being a part of IGH and CCM is a great opportunity to work alongside researchers of varied disciplines (microbiology, pharmacology, epidemiology, etc.) and get a feel for the subjects at the regular meetings.

Effects of mitonuclear interactions on whole organismal metabolic rate in response to multiple stressors – Dr. Avishikta Chakraborty (University College London)

Mitochondria carry their own genome, which mutates at different rates compared with the nucleus, potentially generating mitonuclear incompatibilities over generations and lead to defective phenotypes. The aim of this project is to use ‘mitonuclear’ fly lines to determine how such incompatibilities can affect an animal’s overall energy expenditure when subjected to metabolic stressors known to affect mitochondrial function.

Energy expenditure is central to life. Organisms need to expend energy for physiology, behavior, ecology and a range of life history traits. Despite being of such critical importance, not much is known about the mechanisms underlying metabolic rate in animals. Cellular energy in the form of ATP is produced by mitochondria in the cell through oxidative phosphorylation. Since many physiological and behavioral traits rely on metabolic function, mitochondrial dysfunction can affect wide range of physiological traits in animals. Furthermore, mitochondria possess their own DNA (mtDNA), which is maternally inherited and interacts with the nuclear DNA to support mitochondrial function. Mutations affecting either genome have major effects, creating incompatibilities across proteins comprising the electron transport system (ETS), which can have sex-specific effects due to their differing inheritance. These mutations can lead to a plethora of downstream effects, such as alterations in ATP synthesis, Krebs cycle flux, gene expression changes, along with growth and signaling processes. Mitonuclear mismatches have been further shown to alter crucial fitness-related traits like fecundity and lifespan, in a sex-specific manner. Past work has shown that the intergenomic coadaptation between nuclear and mitochondrial DNA regulated whole organism metabolic rate in birds and insects. However, there is little understanding of the mechanics behind how these mismatches mitochondrial and nuclear DNA can impact whole-animal function, notably at the level of metabolic rate, and other linked physiological processes such as locomotion and sleep in males and females. Most importantly, it is not yet known whether interventions inducing metabolic or dietary stress will have different impacts depending on the mitonuclear context. Answering this question will provide us with crucial information regarding the genetic basis of sex differences and how health interventions can be fine-tuned to differences in mitonuclear haplotypes in humans.

 In our lab, we have generated three Drosophila melanogaster lines, each with isogenic nuclear DNA paired with either the co-evolved mtDNA (WT line) or one of two mtDNAs differing by a few single nucleotide polymorphisms (COX and BAR lines). The student will first establish how metabolic rates differ across these lines under standard rearing conditions (“control”, standard rearing food), between males and females, measure their baseline activity, sleep and climbing behavior. Then, the student will rear the flies and expose them to different dietary treatments targeting mitochondrial function: a high-protein diet (affecting Krebs cycle flux and input of reducing equivalents to mitochondria), a diet enriched in N-acetyl-cysteine (NAC, a precursor of glutathione, acting as an antioxidant), and Nicotinamide Riboside (NR, a precursor of NADH that inputs electron mainly through Complex I in mitochondria). Measurements will be done at three timepoints during the flies’ lifespan to look at the effects of age on these traits.

This project will be highly beneficial to a student with interests in evolutionary biology, metabolism, and disease. The student will learn the basis of fly maintenance (a highly useful animal model) and basic to intermediate statistical analysis in R (ANOVA, lrtests, linear modeling etc.). The new metabolic rate measuring instrument (MAVEN) is user-friendly, and it has in-built macros to transform the data for further statistical analysis. Postdoc support will be available to the student throughout the project. The project has high probability of generating considerable data which can be an independent scientific article. This project will also serve as a platform for the student to broaden their horizon in the field of mitochondrial physiology that has wide applications in biomedical disciplines.

Epigenomic elements associated with physiological cardiac hypertrophy in human and mouse – Dr. Diego M. Fernandez Aroca (Queen Mary, University of London)

Physiological cardiac hypertrophy associates with lifestyle and environmental factors (such as exercise and high-altitude adaptation). However, how gene regulation contributes to this process remains unclear. Here, we will apply genome-wide techniques in mouse and human models to identify regulatory regions associated with the development of cardiac hypertrophy in healthy individuals.

Cardiac hypertrophy is a complex process, often related to lifestyle and environment factors, providing an excellent model of epigenomic regulation. While pathological hypertrophy is a risk factor for life-threatening conditions such as heart failure, benign cardiac hypertrophy is developed under normal physiological conditions (e.g. in response to exercise or high-altitude environments). Although genetic populations studies implicate non-coding regulatory regions in the development of pathological cardiac hypertrophy, the role of epigenomic regulation in physiological hypertrophy has been poorly studied to date, especially using genome-wide technologies such as epigenome profiling. Thus, which epigenomic regions are critical for the development of physiological hypertrophy is largely unknown both in humans and mice. We propose to analyse the epigenomic regulation of physiological hypertrophy using mouse in vivo and human in vitro models.

How environmental inputs influence gene regulation and cellular phenotypes is a fundamental research question in the BBSRC remit. In this project, an increased understanding of cardiac gene regulation conducive to physiological hypertrophy holds the potential to reveal novel epigenetic mechanisms underlying cardiac hypertrophy and address the health implications of lifestyle and environment factors. This work could also contribute to dissect the biological differences between pathological and physiological cardiac hypertrophy.

Task 1: Mice will be exposed to high intensity exercise to generate an in vivo model of physiological cardiac hypertrophy. The student will employ heart samples to conduct epigenome profiling with the cutting-edge technique Cut&Run, and analyse the regulation of histone marks (e.g. H3K27 acetylation). This task will provide novel epigenomic regulatory elements associated to exercise-induced in vivo cardiac hypertrophy.

Task 2: As a complementary approach, the student will use a genetic model of high-altitude adaptation in human iPSCs engineered in our lab with EPAS1 or EGLN1 mutations, as observed in human populations living at high altitude. Control and mutant cells will be differentiated to cardiomyocytes using established protocols. Then, the student will analyse: i) cell size and shape by high throughput microscopy and ii) epigenomic regulation through Cut&Run. This task will provide mechanistic insights into epigenetic regulatory elements associated with high altitude-induced cardiac hypertrophy.

The student will acquire both wet and dry lab highly transferable skills, useful for the student’s future career, getting acquainted with: i) both in vivo and in vitro sample handling; ii) state-of-the-art epigenomics techniques; iii) computational analysis; iv) high throughput microscopy, including the use of advanced machine learning pipelines for cellular segmentation. In addition, the student will be able to develop communication skills through lab meetings and will benefit from EpiHub (http://qmulepigenetics.com/) exposure, enabling the student to begin network connections.

An imaging pipeline for the assessment of mitochondrial dynamics in cochlear hair cells – Dr. James O'Sullivan (King’s College London)

In the inner ear, hair cells (HCs) are organised such that each cell detects a unique frequency (tonotopy). We do not understand the specific mechanisms that regulate development of tonotopy in the embryo. This project will investigate whether differences in the size and shape of specialised structures called mitochondria play a role establishing tonotopy.

The shape and size (morphology) of mitochondria are regulated through the opposing processes of fusion and fission, which can influence cell fate decisions during embryonic development. We seek to investigate whether this is the case in auditory hair cells (HCs) of the developing chick cochlea. Within the cochlea, HCs are organized in an array with large, high-frequency detecting cells at one end (the base) and smaller, low-frequency detecting cells at the other (the apex) in an arrangement called tonotopy. We want to find out if high-frequency HCs have different mitochondrial morphologies to low frequency HFs and, if so, when such differences emerge.

High-frequency HCs are more vulnerable to damage due to age, noise and antibiotic treatment, all of which cause high frequency hearing loss. Because there are no existing therapies to replace HCs, any resulting hearing loss is permanent. Furthermore, mitochondria are critical in transducing the damaging insults that lead to cell death. Regenerative therapies which address this frequency-specific hearing loss require that we identify the signals and molecular mechanisms that control how tonotopy develops. Mitochondrial morphology has recently emerged as a key regulator of excitable cell fate yet remains uncharacterised in auditory HCs.

Due to its high lateral resolution, transmission electron microscopy (TEM) is the “gold-standard” for accurately measuring the morphology of mitochondria. We will prepare samples from high- and low-frequency regions of the cochlea at three developmental timepoints: embryonic days 8, 10 and 14, representing early, middle and late stages of HC development. Samples will be imaged using TEM and the resulting datasets will be used by the student to develop and optimise an imaging pipeline for measuring mitochondrial shape. The student will then be trained by JO to use the machine-learning based WEKA segmentation plugin in ImageJ to segment mitochondria from surrounding structures in the HC. They will test a variety of training parameters and generate a “classifier” which can then be applied across experimental conditions. The student will use their pipeline to generate a quantitative analysis of mitochondrial size and shape in HCs from different cochlear regions throughout development. The student may choose to frame the results in a hypothesis-driven manner – for instance by positing a null hypothesis that mitochondrial morphology will remain consistent over time and region.

The student will gain training and hands on experience using machine learning for image analysis. They will learn how to apply statistical methods such as principal component analysis to examine subcellular morphology. The student will learn the biological principles of several subject areas, will engage in discussion of research during journal club and will present their work to others in the group lab meetings. In addition, the student will be credited with authorship on any future publication or presentation in which the analysis pipeline is used.

The role of mitochondrial health during asymmetric division – Dr. Jens Van Eeckhoven (University College London)

Not only are mitochondria the power houses of the cell, they also help with communication within the cell. For instance, by generating reactive oxygen species (ROS), mitochondria have been known to signal a cell to die. The project will investigate a division where one cell inherits disproportionately fewer mitochondria, yet subsequently dies using a fluorescent protein that is sensitive to ROS.

The Scientific Question

Asymmetric cell divisions are thought to make use of biased protein, RNA and/or organelle inheritance to generate cellular diversity. The latter is difficult to prove and investigate however, as organelles are challenging to manipulate. Using in vivo super resolution microscopy in the model organism C. elegans, we investigate the asymmetric division of a neuroblast in which one daughter cell is fated to die. This daughter cell inherits disproportionally fewer and morphologically distinct mitochondria. This project will investigate whether these mitochondria represent older and/or more damaged specimens.

Why is it important?

From cancer cells that do not stop dividing, to neurons that may no longer divide; cell division and cell fate decisions are core biological phenomena that relate to many diseases. Mitochondria have roles in cancers, as ‘mtDNA [mitochondrial DNA] is among the most mutated regions of the cancer genome, undergoing somatic mutation in approximately 50% of all tumors’ (Kim et al., 2022); and neurodegenerative diseases, as ‘[...] there is strong evidence that mitochondrial dysfunction occurs early and acts causally in disease pathogenesis’ (Lin and Beal, 2006). Studying the role of mitochondrial inheritance in the context of cell fate decisions and apoptosis could lead to the development of mitochondrially targeted therapies in cancer and neurodegenerative disease.

Experimental Approach

C. elegans is a genetic model system, allowing for the tagging of proteins and organelles with fluorescent proteins, which can be imaged live through its transparent body. The student will tag mitochondria in a specific cell lineage with the MitoTimer fluorophore. MitoTimer fluoresces green when it is first synthesized in the cell, and irrevocably shifts towards red fluorescence when it is oxidized by reactive oxygen species produced by mitochondria (mtROS). As MitoTimer oxidizes through mtROS over time, the higher the red-to-green signal ratio we find on a mitochondrion the older that mitochondrion will be. The student will perform ratiometric and image analysis to investigate whether the cell that is fated to die inherits proportionately more mitochondria that have a higher red-to-green ratio (older mitochondria). The student will be involved in and learn about experimental design, vector design, transgenesis, Mendelian genetics, confocal imaging, image analysis and biostatistics.

This project will expose the student to an exciting research environment where they will be encouraged to participate in critical thinking, problem solving, scientific reasoning and state of the art research. The student will gain core molecular biology skills, gain knowledge on C. elegans genetics and genetic tools, gain hands-on experience with confocal microscopy and image analysis, and gain statistical knowledge. This project will provide a unique and varied research experience to the student.

Learning to live together: the importance of early life touch in the development of social behaviours – Dr. Laura Andreoli (University College London)

Neonates requiring intensive care spend many hours in incubators: a place where they lack proper maternal and physical interaction. To what extent this event will impact on the child's sociability and cognitive wellbeing is still not clear. Thus, we propose a study where we use animal models to investigate the consequences of early life touch deprivation in the development of social behaviours.

Touch is crucial to the survival of newborn mammals. Early life touch, generated through physical interaction between pups and with their mother, is important to the development of mature pain responses as well social behaviours such as maternal bonding in both rodents and humans. Thus, altered early life touch experiences including neonatal intensive care can evolve into debilitating conditions in adulthood, affecting physical and mental health. Previous work has largely focused upon the effects of early life experience of sensory-evoked behaviour including reflex sensitivity, but it is yet unclear how this can impact social behaviours, which are critical indicators for a good quality of life. We propose that early life touch is necessary for the development of social behaviours in the mouse.

We will use advanced molecular genetic techniques to silence peripheral somatosensory touch pathways in neonatal transgenic mice, whilst simultaneously recording huddling behaviour using video tracking and machine learning. We hypothesise that in the absence of touch, social bonding between pups will be reduced. The findings of this project will therefore provide a basic understanding of how dysfunctional early life somatosensory experience can alter social behaviour.

To genetically control primary afferent activity in vivo, we will use VGluT1-Cre transgenic mice in order to target Aβ-myelinated primary afferents that transmit innocuous touch, and a Cre-inducible adeno-associated viral vector coding for the inhibitory hM4Di Designer Receptor Exclusively Activated by Designer Drugs (DREADD). In newborn mice, the genetic insertion of the receptor in the primary afferents will be achieved via intraplantar injection of the virus. Starting from the second postnatal week, the time when huddling behaviour arises, afferent activity will be manipulated in vivo by daily intraperitoneal injections (for five days) of the DREADD ligand clozapine-N-oxide. After each injection, huddling behaviour of freely moving pups will be recorded for 1 hour. Recordings will be analysed offline using Ethovision software and DeepLabCut (DLC).

We propose the following milestones: week 1, developing of DLC model; weeks 2-4, video recordings of experimental and control pups; week 5-6, offline pose estimation; week 7, data analysis; week 7-8, preparation of final write up and presentation.

This project will provide firsthand experience of what is involved in the scientific process and how to work in an interdisciplinary team of researchers. The trainee will learn how to correctly select and use animal models in research, as well as to detect and quantify observed behaviours including the importance of statistics. Moreover, by reading selected literature and actively participating in the project discussion with the supervisors and weekly journal clubs, the student will develop a deep knowledge of the subject area and learn the skill of critical assessment.

Machine learning for adaptive optics in deep brain imaging – Dr. Thomas Smart (University College London)

Adaptive optics (AO) is a technology that allows us to collect high-resolution light-based images from turbid material such as brain tissue. AO works by tuning an adaptive optical element to compensate for aberrations induced by the sample and restore sharpness and brightness to a blurred image. This project will investigate machine learning as a tool for optimising image quality in an AO system.

The scientific question

To understand the function and morphology of neural cells in the mammalian brain, we require a tool that allows us to non-invasively visualise those cells in physiologically relevant conditions. Our research requires high-resolution images from deep within the brain. Optical microscopy offers high-resolution imaging but collecting light from deep tissue is challenging.

Traditional optical microscopes are limited to use near the tissue surface. At greater depths, light scattering blurs the images. Microscopy techniques that use nonlinear light-matter interactions to generate images (e.g. two-photon microscopy) have special features that make them less sensitive to scattering and are thus well suited for imaging in tissues.

Even so, the performance of these methods is hampered by sample-induced optical aberrations. To overcome these, we can use an adaptive optical element such as a deformable mirror (DM) to correct the image. This technique is known as adaptive optics (AO). Image-guided AO uses a merit function (e.g., image brightness) to quantify the quality of the image. The shape of the DM is adjusted in an iterative manner to maximise the merit function and improve the quality of the image. This procedure is relatively slow, however, and risks photobleaching the tissue.

The objective of this project is to investigate Deep Reinforcement Learning (DRL) for image-guided AO control. This will allow faster and safer aberration correction which is important in dynamic samples, such as live brain imaging.

Why is it important?

Improving the resolution of functional and structural imaging through AO has the potential to improve interrogation of signal propagation and inter-neuron communication in the brain. Dendritic, axonal and synaptic structures are often neglected due to their small size, despite being integral to neural computations and learning. Uncovering how signals propagate through these structures may uncover pathological conditions and the effects of novel therapies.

Experimental approach

The initial part of the project will be to computationally simulate the effects of aberrations. Next, the simulation will be expanded to include the effects of an DM to correct aberrations and restore image quality. The simulated AO environment will be used to train a DRL network, allowing the network to shape the DM to optimize the merit function. The project will conclude by testing the trained DRL network performance on a real imaging system using a tissue phantom.

This is an excellent opportunity for a student to develop their skills in valuable areas such as optical microscopy, optical aberration theory, computing, machine learning, and mathematical modelling. This is also an opportunity to work in a stimulating environment at a world-leading research institute for vision science. Our group enjoys collaborations with several other research teams across UCL, and at many other internationally recognised universities. Experience in our lab should enhance the student’s confidence when considering postgraduate applications, whether in academic research or industry.