Please join us online, Thursday 18th May, from 15.00-16.00 for this 2nd edition “Become a bioengineer during your medical training”
This new series of webinars, called Future Leaders in Convergence Science, brought to you by the Cancer Research UK Convergence Science Centre at Imperial College London and The Institute of Cancer Research, will give a platform to our PhD students to present their research, and share their experience of navigating between disciplines and finding their scientific identity as convergence researchers.
Hosted by Professor Rylie Green, Head of the Bioengineering Department, Imperial College London.
“Bioengineered tumour-targeted interleukin-12 for tolerable and personalised immunotherapy combinations”
Interleukin-12 (IL-12) is a highly promising pro-inflammatory anti-tumour cytokine. Unfortunately, its inability to penetrate the stroma of solid tumours leads to peripheral toxicity. The Ishihara lab previously conjugated IL-12 to a collagen-binding domain (CBD), a molecule with high affinity for collagen. CBD successfully delivered its IL-12 payload into highly collagenous stroma of breast, colon, and melanoma mouse models and suppressed tumour burden. To minimise toxicity and ensure the IL-12 is exclusively active in the tumour stroma, we masked CBD-IL12. The mask is attached to CBD-IL12 using a protease-sensitive protein linker. The linker was found to be cleaved in vitro by tumour lysate in a time-dependent manner and not by serum, suggesting a degree of tumour-dependent activation. This bioengineered molecule was tested in colorectal, breast, and pancreatic cancer mouse models. Masked CBD-IL12 triggered complete responses in breast and colorectal cancer models and significantly prolonged survival. Although it did not prolong the survival of mice with pancreatic cancer, it considerably reduced their number of liver metastases. In doing so, it triggered significantly less toxicity than wild-type IL-12 in all these models, suggesting the mask is suppressing IL-12 related toxicity. Masked CBD-IL12 seems to be a novel promising bioengineered molecule, particularly efficacious with reduced toxicity in treating different cancer types.
Melanie interrupted her Bachelor of Medicine and Bachelor of Surgery (MBBS) to undertake a convergence science intercalated PhD. She previously obtained an intercalated BSc in Medical Sciences with Immunity and Infection at Imperial College London. She is a member of the Ishihara lab at Imperial College London and the Sadanandam lab at the Institute of Cancer Research.
“Improving endometrial cancer diagnosis via detection of microRNA biomarkers from liquid biopsies: From biomarker discovery to screening test engineering”
Endometrial cancer (EC) is the second most common gynaecological cancer worldwide. Despite such ubiquity, diagnosis involves trans vaginal ultrasound (TVUS) an invasive procedure which many individuals must undergo due to the non-specific symptoms of EC. There is also a dearth in clinically useful validated biomarkers, making it difficult to develop new investigations to diagnose EC. A new investigation is required to accurately diagnose patients, ideally one that fits the WHO ASSURED criteria which will also require a novel set of biomarkers to detect. Lateral flow tests (LFTs) and other microfluidic paper-assay devices(uPADs) are cheap, easy to produce assays. They can be used to detect a variety of biomarkers and diagnose several conditions, offering a potential platform upon which to develop a diagnostic tool for EC. MicroRNAs (miRs) are potential biomarkers that could be used to diagnose EC. A family of short non-coding RNA molecules, miRs play a vital role in regulating cell function, signalling and proliferation. Hundreds of miRs are differentially dysregulated in a variety of cancers. However, the discovery and use of miRs as clinically useful diagnostic biomarkers for EC has been hindered by technological challenges including, multi-step, error prone detection methods and lack of individual miRs with strong negative or positive predictive values. The goal of this PhD project is to:
For both devices we have incorporated novel technologies and techniques including oligonucleotide templated reactions using peptide nucleic acid (PNA) probes and we plan to utilise original denaturing hydrogels, which should allow us to achieve the above stated goals.
Daanyaal Khan is an iPhD student funded by the CRUK convergence science centre. He is based in Dr Sylvain Ladame's team at the department of Bioengineering and Professor Sadaf Ghaem-Maghami's team in the department of Surgery and Cancer, both at Imperial College London. His current research interests revolve around novel circulating biomarkers and translating these to development of clinically amenable diagnostic devices.