Research Projects 

Project description

In the heart, function and structure are intricately related, therefore, to understand the formation of arrhythmias, we need to investigate cellular electrophysiology within its native structural environment. Optical methods based on multiphoton microscopy are ideally suited as they are non-invasive and robust in scattering tissue. This project will develop novel optical technology to investigate electrical activity deep within the wall of the heart chamber to probe cardiac conduction transmurally in health and disease. The NHS highlights that 2 million people are affected by abnormal heartbeats, or arrhythmias, in the UK per year. This project will establish a novel perspective in cardiac electrophysiology by enabling systematic and direct investigations of cardiac excitation waves and develop far reaching technology with wide applicability in the development of diagnostic and therapeutic interventions to tackle a global health issue. 

The key research question is deceivingly simple: how do electrical wavefronts propagate through the thick muscular wall of the heart? This question has far-reaching implications in studies of healthy and arrhythmic hearts, yet remarkably, we lack an answer due to the insufficient penetration depth of non-invasive optical measurements of electrical activity through several millimetres of ventricle wall. This PhD project will inform the following question: is remote focusing, a technique to achieve fast axial scans without perturbing the sample, a suitable method to track action potentials “transmurally”?

Figure 1: Preparation of living left ventricular rabbit cardiac slices and a TTC-stain based viability test.

“This project is strongly interdisciplinary in nature and relies on nonlinear optics, ultrafast lasers, imaging and microscopy, cardiac electrophysiology, voltage sensitive dyes and remote focusing techniques. It offers Giedrė the opportunity to acquire a wide range of skills and work at the interface of optical technology development while gaining valuable insights in cardiovascular science which will not only greatly enhance the immediate impact of her research but also train her in “biological” language, concepts and research methodologies. This capacity building will be priceless for any scientists wishing to bridge the gap between technology and life and prepare them for a successful career either in industry or in academia. This project further comes with the opportunity for Giedrė to spend some time abroad in the labs of Dr Sacconi in Florence, Italy. In addition to capacity building by working in a foreign laboratory to learn best practices and novel research approaches, she was able to learn specific skills highly relevant to microscope development and her own research project.”

Dr Caroline Müllenbroich

Figure 2: Experimental setup of the 2-photon microscope with custom-built remote focusing module and dispersion compensation units.

“I like that in my project I can learn a wide range of skills from imaging system development to advanced biological sample preparation protocols. I enjoyed the collaborative environment and knowledge exchange fostered by the Extreme Light and Imaging Concepts Groups, where diverse expertise comes together to push the boundaries of what microscopes can achieve. I had a chance to join measurements on other systems, expanding my expertise other modalities of optical microscopy.

I chose to pursue an interdisciplinary project because of my passion for working at the intersection of physics and life sciences. This has been particularly rewarding, especially during experiments with living cardiac preparations, where I could observe the muscle slices contracting in response to electrical stimulation, and visualise the propagating electrical wavefronts with voltage sensitive fluorescent dyes. As the same processes are essential to sustaining life and occur within our own bodies, it always brought me a sense of awe!

Although rewarding and exciting, I found it challenging to learn subjects outside my specialism (physics) and developing the communication and management skills needed to advance a cross-disciplinary project. For example, when discussing results with cardiovascular science collaborators, we had to find a common language to troubleshoot aspects of both the optical system (aberrations) and the biological sample (pH of the buffer solutions). Furthermore, management and communication were essential to coordinate the experiment days efficiently when a living sample was involved.”

Giedrė Astrauskaitė