There are so many fantastic scientists at Abcam who are truly experts in their field, so we wanted to highlight some of the achievements some of them have made throughout their careers. These may be a hugely impactful paper they have published, a method they developed, or even something that meant a lot to them personally which they want to shout about. Read on to find out about some of these fantastic achievements.
Team Leader in SciQC, Product Portfolio and Innovation
Evolution in a test tube: HIV-1 evolves to resist a monoclonal neutralizing antibody
Like many of you, I have spent many (some say too many) years in the laboratory. Thinking back on it, most of these were spent chasing publication, grants, repeating experiments and attempting to make a difference. And a few times, I had that spine-tingling excitement, when things worked - and it was almost difficult to go home at night.
Which of my many projects did I enjoy the most? Without a doubt – forcing HIV-1 to evolve in a test tube (OK – a tissue culture plate) – under my watchful eyes, as it mutated to evade neutralizing monoclonal antibodies (NMAbs). This helped us understand how the virus changed to overcome the assault of the NMAbs on the amino acid level.
As C8166 cells undergo syncytia (“blobbing”) upon HIV-1 infection, I could observe infection under the microscope, making my life easier. By challenging the virus with gradually increasing levels of three different NMAbs, I succeeded in nursing the HIV-1 cultures and finally had viruses that could infect cells in the presence of very high concentrations of NMAbs. When I managed to identify the aa changes, reclone these and confirm that the new virions were indeed resistant, I was buzzing. This gave a binding profile of the Abs and highlighted how easily HIV-1 could overcome antibody-mediated neutralization. I observed Darwinian evolution in a test tube!
The paper was finally accepted (you can read it here) in a rather low impact journal, has only been cited three times, and will never be regarded as my most important piece of work. But I loved it!
General Manager, R&D Leadership
A serendipitous discovery: flow lithography
Microparticles are used in a broad range of applications from the purification of industrial reagents to the diagnosis of disease. Historically, such particles were limited to spheres with a single functionality (ie beads). During my PhD at MIT, I broke this paradigm, discovering an entirely new method to manufacture microparticles that combined lithography, commonly used to print computer chips, and microfluidics, the flow of liquids on a microscopic scale. This approach, dubbed “flow lithography,” can be used to make particles of virtually any size, shape, or functionality. Unbeknownst to most, the approach was also the direct result of a “failed” experiment for another project I was working on.
To date, the two seminal papers describing flow lithography, published in Nature Materials and Science, have been cumulatively cited more than 1500 times. The approach has also formed the foundation of two start-up companies, Firefly BioWorks, and Motif Micro, which have both been acquired by larger companies.
Product Specialist, Primary Conjugates
You are what your mum ate: impact of maternal obesity on the cardiovascular health of the offspring
Obesity is a health problem of pandemic proportion, which arises from an imbalance between energy intake and energy expenditure. Recent statistics have highlighted that 50% of women of childbearing age are overweight or obese in the UK, with a similar pattern in other countries. This is of concern as being obese during pregnancy has been shown to be detrimental not just to the mother’s health but also impacts on the baby. This has been termed “developmental programming” and suggests that development in an in utero obesogenic environment “programs” an increased risk of obesity and cardiovascular disease in the offspring, such as high blood pressure and heart failure in the long term.
During my PhD at the Wellcome Trust-MRC Institute of Metabolic Science in Cambridge (UK), using a combined approach of physiology and molecular biology, I looked at the consequences of maternal diet-induced obesity in adult offspring. Our results show that an unhealthy diet during pregnancy poses an increased risk of cardiovascular diseases in the offspring, independently of offspring eating a healthy diet throughout their life. Improving our knowledge of the detrimental effects of obesity during pregnancy is urgently needed to design effective intervention strategies for the mother and the baby.
These findings are now published and you can read the paper here.
Site-directed mutagenesis is a technique that has been used in life science research for decades. The technique allows you to change individual bases in a nucleotide sequence, for example, changing a Guanine (G) to a Thymine (T). The method is commonly used to investigate the biological function of the protein or RNA encoded by the altered DNA sequence. However, the original methods for doing this were very unreliable and could be incredibly time-consuming. This encouraged me to develop the methodology for QuikChange mutagenesis.
QuikChange is now over 20 years old and still the number one way of doing site-directed mutagenesis. The kits are found in almost every institute all around the world, and the technology has helped accelerate countless research projects across the globe. You can read the original paper describing the method here.
The future of agriculture: identifying genetic wheat variants
With increasing demands on the quality and quantity of food required, we need improvements to current agriculture practices. Increased food production requires more agricultural land, pushing crops into non-traditional areas. The need for advances in agricultural technologies is not only necessary for current crop varieties, but also for new varieties with increased tolerance to environmental stresses. Technological improvement means better crop yields and reduced land, water, fertilizer, and pesticide use.
In my previous work, I used microarrays to analyze genotypes for single nucleotide polymorphisms (SNPs). Wheat diversity was examined to identify polymorphic markers between various wheat cultivars for use in marker-assisted breeding programs. Microarray analysis was shown to discriminate between tissue samples from wheat cultivars grown under various environmental stresses. Polymorphic markers were identified between samples treated with differing salt, light, and temperature conditions.
The identification of trait-linked molecular markers, such as salt resistance, allows plant breeders to genotype individual plants and populations to determine the most suitable cultivar to plant that best complements its local environment. This eliminates the need for multiple planting cycles to optimize crop selections and gives the plant breeder the highest possible chance for crop success (yield, quality, performance, and cost).
Quality Control Associate, in-house Manufacturing
I-TASSER: protein structure prediction made easy
During a project focusing on genome comparisons between arthropod bacterial parasites, we were able to identify suspected gene families and their approximate function using the I-TASSER protein structural prediction toolset, enabling us to identify the genes based on identical structural matches despite the lack of nucleotide or peptide homology.
The proteins had initially been suspected to be part of a family due to shared sequence regions, but tools such as BLAST and BLASTP were unable to find a match. Another protein of interest not related to the suspected gene family had notable areas of repeats, but the only matches were poor-significance matches to ice nucleation proteins in plant bacteria. However, after applying the I-TASSER pipeline, we found structural matches that were within an angstrom average difference of the best-fit match in UniProt, revealing the gene family to be a likely family of membrane-bound metal transport proteins, with the shared region between the family being a distinct twist and ion binding site.
This method of functional identification and family identification using protein structural prediction could be applied to other species, as many bacterial species contain a high percentage of unknown-function proteins that may be able to be identified and grouped using this method. The work I mention here has just been accepted for publication and will be available to read very soon.