Dr. Mandë Holford, Marine Chemical Biologist

What can we learn from venomous marine snails? Join Dr. Mandë Holford as she discusses how scientists discover new things from extreme creatures of nature!

By American Museum of Natural History

Dr. Mandë Holford’s Office in Belfer Research Building

 Mandë is a marine chemical biologist. She studies the evolution of venomous sea snails and the function of their venom in manipulating cell signals related to pain and cancer. The snails she studies have venom like snakes and they prey on fish, worms, and other snails. 

Mandë is an Associate Professor at Hunter College with a scientific appointment at The American Museum of Natural History (AMNH) and Weill Cornell Medical College (WCMC). Mandë has lab space at Hunter and AMNH that she uses to conduct different research. 

This is her office at the Belfer Research building which is a collaborative research space for Hunter and WCMC scientists.  

Shelf of reference materials

This bookshelf holds a lot of Mandë’s reference materials. Being a scientist means being a lifelong learner. As you ask more questions, you learn more skills and keep building your tool kit. 

These books highlight the interdisciplinary research in the Holford group as they cover chemistry, biology, and snail taxonomy and evolution.  

Shell from dive

This shell is from Mandë’s first expedition to collect venomous sea snails in Panama. It reminds her of all the things she learned such as that the shells bury themselves in the sand and you have to recognize the sand trail to dig them up. 

Also, night time is usually the best time to collect as these snails are nocturnal feeders and so they don’t hide in the sand when coming out to feed at night. 

Antique science equipment (Liquid Nitrogen Dewar)

This is an antique liquid nitrogen dewar. Liquid nitrogen is colorless clear liquid that is extremely cold (-320 F). Scientists use it to instantly freeze things and to store samples that need to be kept frozen such as cell lines. 

Mandë’s first research project involved working with lasers, and liquid nitrogen was used to keep the lasers cool. 

She couldn’t believe thinking creatively and using your imagination to figure out how proteins pump hydrogen was a job you could get paid for… being a scientist is fun! 

Dr. Mandë Holford’s Belfer Laboratory Bench Area

Generally, Dr. Holford spends her time in this space working with her team of undergraduates, graduate students, and postdoctoral scholars to conduct research experiments.

Dr. Mandë Holford’s Belfer Laboratory Bench Area

Each lab member has their own desk and work “bench” (That’s what they call the long tables they use to work on).

In the Holford lab, graduate and undergraduate students work together. The full team works hard discovering new knowledge about venomous snails and how components in snail venom can be used to learn more about the basic function of cells. 

Biological and Bioinformatic Analysis

The bench behind Mandë is where lab members who do more biological experiments and bioinformatic analyses sit. These students run gels, extract DNA and analyze computational data. 

Chemical Characterization Experiments

The space shown here is for lab members who do more chemical characterization experiments.  These students are weighing out amino acids to synthesize peptides or preparing cells for studying functional activity of the peptides. 

Equipment on the benches

These analytical scales, microscopes and glassware are some of the tools scientists use to discover new things, move the field forward, and innovate how they think about venom or drug discovery. Each piece of equipment is used for a specific task.

For example, graduated cylinder are used to measure large amounts of liquids and beakers are used to measure small amounts of liquid.

Dr. Mandë Holford’s Analytical Procedure Room

This is an instrument room where Mandë’s research group characterizes and synthesizes venom components. After an expedition, they will dissect a piece of snail tissue from the venom gland or the foot and extract RNA or DNA to learn more about the snail and its venom.

If the experiments are further along, the team will use this room to characterize peptides found in the venom or analyzing data. 

HPLC machine which characterizes components in the venom

This machine is a cutting edge tool that allows scientists to characterize the individual components within snail venom-there could be over 200 individual components! 

The UHPLC (Ultra High Performance Liquid Chromatography) machine separates components based on hydrophobicity (liking water). Components that like water are separated first, and components that don’t like water are separated last.

Like ink bleeding into a piece of tissue paper, the ink leaves a trail as it moves across the paper and separates into different blotches. 

By collecting each blotch separately, scientists can identify each venom component and test the effect each has on the manipulating cell signals. 

Gel Imaging Apparatus

Each snail makes very small amounts (nanograms) of venom, so in order to get enough venom peptides to study the lab has to make the peptides synthetically. 

To do that you have to identify the peptide sequences by extracting DNA or RNA from a snail tissue. Once you’ve extracted the DNA material you can visualize how much DNA you have and how pure it is by running a gel (think jello things of different masses to separate them). This machine is used to visualize the gel. 

Team work makes science more effective

When pursuing scientific questions it helps to get opinions from diverse voices, as everyone tackles problems from different perspectives.

Eric, a first year graduate student at the City University of New York Graduate Program, and Corina, a sophomore student at Hunter College, are analyzing data from the UHPLC. 

Experiments don’t always work so you have to stop and think: What now? You have to look at the results and see what evidence you can use to tweak your strategy for next time.

Real time PCR machine

The Polymerase Chain Reaction (PCR) machine revolutionized molecular biology.

It amplifies a small amount of DNA to produce millions of copies of a specific gene or region that can be used for DNA based phylogeny building, which is how the Holford group builds the snail phylogeny (think snail family tree), that they use to identify specific snail species to work on. 

Kary Mullis won the Nobel Prize in 1993 for creating the PCR machine. Part of being a scientist is devising new methods or new technologies and being proactive.  

Molluscan Collections of the AMNH

When a scientist goes on an expedition to collect specimens, they need to store (voucher) their collections somewhere. Natural history museum collections are historically used to catalog biodiversity found on our planet.

When the Holford lab goes on an expedition they voucher some of their snail shells in the molluscan collection at AMNH. 

Terebrid shell (Auger snails)

These cabinets hold the terebrid shell collections of AMNH that help us study the taxonomy and evolution of terebrid snails. Tens of thousands of terebrid shells from various expeditions from all over the world are stored in these cabinets. 

After an expedition if Mandë’s team think they found a new terebrid species, they consult the AMNH terebrid collection to make sure the species was not identified before. 

Using shell morphology characters they compare features such as color, size, protoconch (top of the shell), whorls (bands on the shells) to figure out if the suspected new species is really different from the other shells in the collection. 

Shelves of terebrid snail shells

The terebrid shells in the shelves are separated by species. Each species have specific characteristics. Originally, shell morphology was used to that all terebrid shells have a common ancestor in the terebrid phylogeny (snail family tree). 

Terebrid snails are often called auger snails because their shell is shaped like a screw or a drill bit. Some shells are very long and pointy, others are short and squat. 

When trying to figure out the kind of terebrid snail that was collected on an expedition you compare the shell features. To be good at this game you have to be very observant and pay attention to details.

Room 100- lab where shells are inspected

When examining the terebrid shell collection, you remove the shell shelf you’re interested in and take it into this room where there are microscopes, calipers, and computers that help you study the shell features. 

After studying snail shells for a while you learn to recognize specific features that group each shell into a genus (think same breed like dogs). You have to think critically about each feature of the shell and deduce which genus it belongs to. 

Being a scientist is like being a detective in search of clues for how the world works.  

Tall ladder!

Ladders are a great metaphor for science- each rung represents new knowledge. Each time you learn something new about what you’re studying you climb to the next rung. Being a scientist means being a lifelong learner and always trying to reach the next rung. 

You have to believe in you can find evidence and analyze data that will get you up the ladder. So much of what we’re looking for isn’t known, so you have to come  up with new theories to explain natural phenomena.

AMNH Hall of Ocean Life

For many people an interest in science starts when you interact with nature. If you like to going to the beach, swimming, looking at sea creatures from snails to whales, you might be interested in being a marine scientist. 

To be a marine scientist and have a job at a natural history museum, a PhD is usually required. However, a lot of people practice as amatuer scientists by helping identify new species and these folks don’t need a degree. 

Their love of exploration and discovery drives them to learn as much as they can. In the AMNH Milstein Hall of Ocean Life you can learn a lot about marine biodiversity.

Whale

This whale at the AMNH is 94-feet-long and 21,000-pounds. Scientists that studies whales are called cetologists. Cetologists study how whales make their song, how they migrate through the oceans, and how many different species there are. 

These scientists usually major in biology in college, then go to graduate school where they work in labs and make scientific discoveries but even in high school you could intern in a science lab to see if this is a field that would be exciting for you to pursue!

Tree of marine life

This is a phylogenetic tree highlighting the evolution of marine life. As a scientist, you have to be comfortable with not knowing things. 

It involves a lot of trial and error to figure out the laws of nature and what led to the diversity of animals in our oceans to build the phylogenetic tree. 

You have to be tenacious and resilient because many times you have to work very hard to figure out how to build the tree to describe how different species evolved.

Diorama of bioluminescent creatures

The oceans are filled with amazing creatures. This diorama highlights fish that glow! These fish live deep in the ocean and are bioluminescent, which means they produce and emit light. 

Scientists are really excited about these animals because if we figure out how the fish light up we can use that knowledge to figure out how to make other things glow, like the cells in our brains so we can watch how the brain sends signals from one brain cell to another.

To find what makes these animals glow we need to use chemistry, biology, and some physical techniques. 

Killer Snails Headquarters Made in NYC Media Center

Not all science is performed in a laboratory! Mandë loves educating the general public about her research and about the amazing animal biodiversity on our planet. 

She partnered with Jessica Ochoa Hendrix and Dr. Lindsay Portnoy to form a company called Killer Snails to create learning games about extreme creatures (like venomous snails) to innovate how science is taught. 

This co-working space in Brooklyn, New York focuses on Media and Entertainment companies. There is a lot of exciting opportunities for using the skills you learn from training to be a PhD scientist. 

You can use your knowledge in academia, or to do policy work for the government, or to work in industry, or to start a company!

Assassins of the Sea Game

This is a card game in which players are scientists on an adventure to collect predatory marine cone snails. This award-winning learning game was created with the American Museum of Natural History and Playmatics with funding from the National Science Foundation. 

With their first successful game out, the Killer Snail team is working on several new games to engage, excite, and inform the public about Nature and science...stay tuned! 

Filmmaker- Little Sallie Walker

Co-working spaces support people working in a variety of industries. Marta Effinger-Crichlow is an IFP JustFilms Fellow and the Director/Producer of her feature-length documentary film Little Sallie Walker.

Little Sallie Walker is the untold story of black women who hold on to play to survive life in America.

Evolving Technologies Corporation

The Made in NYC Media Center also hosts members such as Evolving Technologies Corporation- a design and media shop focused on creating custom VR experiences. 

They're the tech powerhouse behind various filmmakers and storytellers whose work is showcased at NY Film Festival, Kaleidoscope VR, Oculus and Tribeca.

“Kaleidoscopea 2.0” Digital video by Thomas D. Rotenberg

Co-working locations frequently use common spaces to showcase projects of members such as this artwork. This piece is found footage, edited and transformed into an enveloping, colorful moving wallpaper designed for the Made in NY Media Center’s 360-degree projection system.

Credits: All media
The story featured may in some cases have been created by an independent third party and may not always represent the views of the institutions, listed below, who have supplied the content.
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